Journal of Nanotheranostics doi: 10.3390/jnt7020012

Authors: Aurelie F. Brownsberger Carlie Kudary Hezekiah H. Williams Shirley Wei Philip Latorre Ryan Eastland Olivia Sayani Jichong Lyu Ryan Davey Victoria Hopkins Ryan K. Roeder Prakash D. Nallathamby

Nanoparticles offer a versatile platform for the selective eradication of pathogenic or diseased cells by integrating therapeutic payload delivery with precision targeting. Precision targeting can be achieved (1) actively through ligand conjugation, (2) passively by exploiting the physiological abnormalities of diseased tissues, or (3) intrinsically through the innate biophysical properties of the nanoparticle. Intrinsically selective nanoplatforms (iNPs) are particularly advantageous when the disease-promoting agent does not possess distinct surface markers, such as in the case of certain “untargetable cancers” or cancers without known targets. Indeed, nanocarriers for chemotherapeutic or gene delivery have achieved selective cancer cell apoptosis without requiring marker presentation, thereby expanding the therapeutic window of the payload. Disease-promoting agents whose physical properties are different from those of healthy cells are also good candidates for intrinsic nanoparticle targeting. For example, antimicrobial nanomaterials have been designed to disrupt bacterial membranes and reduce the risk of antimicrobial resistance by leveraging stiffness differentials between bacterial cell walls and eukaryotic membranes. Nanoparticle systems with intrinsic targeting mechanisms can also enable non-invasive imaging with near-infrared fluorescence, MRI, and photoacoustic imaging for real-time biodistribution tracking and treatment monitoring. This review synthesizes current innovations in nanoplatform design with intrinsic targeting capabilities, spans applications in infectious and non-communicable diseases, and discusses emerging strategies to enhance specificity, overcome resistance, and translate these platforms toward clinical and field deployment.

Journal of Nanotheranostics doi: 10.3390/jnt7020011

Authors: Pooja Tiwary Krishil Oswal Ryan Varghese Pardeep Gupta

Background: Conventional therapeutic and diagnostic approaches, despite improving clinical outcomes, remain limited by poor bioavailability, inadequate targeting, suboptimal pharmacokinetics, and systemic toxicity, particularly in complex diseases. To overcome this, nanomedicine has emerged as a transformative strategy, employing engineered nanoparticles to enhance drug stability, controlled release, targeted delivery, and diagnostic performance, thereby enabling theranostic applications. This review evaluates major nanoparticle platforms in therapy and diagnosis, comparing their mechanisms, applications, and challenges while highlighting their potential to advance precision medicine and theranostic strategies. Method: For providing the context and evidence, relevant literatures were sourced from Google Scholar, PubMed, and ScienceDirect using targeted keywords including “drug delivery,” “diagnostics,” “nanoparticles,” “nanomedicine,” “nano drug delivery,” “nanotheranostics,” “targeted therapy,” “controlled drug release,” “solid lipid nanoparticles (SLNs),” “lipid nano carriers (LNCs),” and “inorganic nanoparticles.” Although no strict time limit was applied during the literature search, clinical trial data were collected and analyzed up to January 2026. Given that clinical trial registries are continuously updated, the included trials represent the status at the time of data retrieval. However, it is pertinent to note that the earliest relevant studies appeared in 1973. Conclusions: This review highlights nanoparticle fundamentals, major material classes, mechanisms of action, and applications in targeted therapy, imaging, and theranostics. It also addresses translational barriers related to safety, scalability, biological complexity, and regulatory compliance. Overcoming these challenges through standardized characterization and interdisciplinary collaboration is crucial for clinical adoption. Future efforts should focus on AI-driven design, computational tools, smart nanomedicines, and advanced biosensing technologies to integrate nanoparticle-enabled precision diagnostics and therapy into routine clinical practice.

Journal of Nanotheranostics doi: 10.3390/jnt7020010

Authors: Jonghyun Park Dongmin Yu Taeho Kim Chanju Choi Simseok A. Yuk Hyungjun Kim

Nanotheranostic platforms integrating diagnostic and therapeutic functions within a single system have attracted significant attention in precision medicine. However, conventional nanotheranostics based on systemic administration often suffer from off-target accumulation, limited retention at disease sites, and dose-limiting toxicity. To address these limitations, hydrogel-integrated nanotheranostic systems have emerged as a promising strategy for achieving localized diagnosis and therapy with improved spatial control and safety. This review provides a comprehensive overview of recent advances in hydrogel–nanomaterial nanotheranostic platforms, focusing on their design principles, diagnostic capabilities, and therapeutic applications. We discuss the complementary roles of hydrogels and nanomaterials, where hydrogels function as localized reservoirs and tissue interfaces, and nanomaterials provide imaging and therapeutic functionalities. Key integration strategies including physical encapsulation, chemical conjugation, and in situ nanoparticle formation are systematically compared. We further summarize localized diagnostic modalities such as real-time imaging and therapy monitoring, and highlight research-driven applications in cancer treatment, inflammation and infection management, and tissue regeneration. Finally, major translational challenges and future perspectives toward personalized, image-guided local theranostics are discussed. Overall, hydrogel-based nanotheranostic platforms represent a versatile approach for next-generation localized precision medicine.

Journal of Nanotheranostics doi: 10.3390/jnt7020009

Authors: Segev Sharon Gayatri Mainkar Lior Zangi

Personalized medicine aims to tailor therapy based on patient-specific molecular and biological characteristics, while nanomedicine focuses on engineering delivery systems to overcome pharmacokinetic and biological barriers. Despite major advances, both fields are limited when applied separately. This review discusses integrating patient stratification with rational nanocarrier design, a combination termed personalized nanomedicine, as a framework to maximize therapeutic index. With emphasis on clinically validated and late-stage examples, we analyze how molecular stratification informs therapeutic design, with particular focus on translational constraints and engineering trade-offs. Results: Personalized medicine enables precise target identification and patient stratification but does not address delivery barriers that limit therapeutic distribution and safety. Conversely, nanomedicine overcomes delivery challenges but exhibits patient- and disease-dependent variability. Merging these approaches allows nanocarrier design to be tailored to disease biology and patient-specific barriers to effective treatment. Recent clinically successful examples demonstrate that co-optimizing biological targeting and delivery engineering can improve translational robustness. Conclusions: Personalized nanomedicine represents a convergence of molecular stratification and engineered delivery systems, a fusion that facilitates context-dependent therapeutic design rather than one-size-fits-all formulations. While significant translational and regulatory challenges remain, treating delivery design as an integral component of personalization offers a viable path toward broader clinical implementation. Continuing to integrate patient profiling with nanoengineering principles will be essential for translating personalized nanomedicine from promising case studies into standard clinical practice.

Journal of Nanotheranostics doi: 10.3390/jnt7020008

Authors: Kamila Rawojć Karolina Jezierska Kamil Kisielewicz

Glioblastoma (GBM) remains among the most treatment-refractory human malignancies. It is characterized by profound radioresistance and a highly immunosuppressive tumor microenvironment, limiting the durable efficacy of radiotherapy. Beyond direct cytotoxicity, ionizing radiation can induce immunogenic cell death and the release of damage-associated molecular patterns (DAMPs), including surface-exposed calreticulin, HMGB1, extracellular ATP/adenosine, and tumor-derived DNA. These signals engage pattern-recognition receptors and cGAS–STING–type I interferon pathways, transiently promoting antigen presentation and immune activation. In GBM, however, DAMP signaling frequently evolves toward chronic inflammation and immune suppression, characterized by myeloid cell recruitment, adenosine accumulation, and immune checkpoint upregulation, thereby contributing to tumor regrowth and radioresistance. This dual immune-regulatory role of DAMPs highlights the importance of temporal and contextual interpretation of radiation-induced immune responses. In this review, we summarize current mechanistic and translational evidence on DAMP-mediated immunomodulation in GBM radiotherapy; discuss modality-dependent considerations across photon, proton, and high-LET irradiation; and evaluate the emerging potential of DAMPs as dynamic biomarkers of treatment response. We further outline how integration of DAMP profiling with liquid biopsy, imaging, and nanotheranostic platforms may support biologically informed and adaptive radiotherapy strategies for glioblastoma.

Journal of Nanotheranostics doi: 10.3390/jnt7010007

Authors: Gabriel Tolardo Colombo Ruan Rompato Vieira Gustavo Sanguino Dias Marcia Edilaine Lopes Consolaro Ivair Aparecido dos Santos Raquel Dosciatti Bini Luiz Fernando Cotica

The usage of magnetic nanoparticles (MNPs), particularly iron oxide-based systems such as magnetite (Fe3O4) and maghemite (γ-Fe2O3), has significantly advanced the field of theranostics. These nanoparticles unite therapeutic and diagnostic capabilities due to their favorable magnetic properties and surface engineering potential. However, the path from synthesis to clinical application poses substantial challenges, including optimization of structure–property–function relationships, biocompatibility issues, and effective surface functionalization. Various synthesis methods, such as co-precipitation and thermal decomposition, aim to achieve specific nanoparticle characteristics, although they encounter obstacles related to scalability and reproducibility. Furthermore, characterizing these systems through structural, microstructural and spectroscopic techniques is vital to determine their functional efficacy and ensure their safe biomedical usage. This review comprehensively examines recent advancements and identifies existing challenges in the clinical translation of MNPs, highlighting the need for refined methods and standardized protocols to effectively exploit their theranostic potential. It outlines future directions, emphasizing the importance of green synthesis and robust characterization frameworks to enhance the integration of MNPs in personalized medicine.

Journal of Nanotheranostics doi: 10.3390/jnt7010006

Authors: Liangzhi Luo Pengjun Sun Tianyi Zhang Ziyao Zhou Tianle Zhang Ziyang Hao

While CRISPR-Cas9 enables precise targeting of cancer-driving genetic aberrations, its clinical application is impeded by instability, delivery inefficiencies, and immunogenicity. Nanotechnology addresses these challenges by engineering nanocarriers that facilitate enhanced cellular uptake, promote efficient endosomal escape, and ensure targeted delivery. This review summarizes current progress in nano-integrated CRISPR-Cas systems for cancer therapeutics, highlighting recent advancements in stimuli-responsive nanoplatforms for precise genome editing and their prospects for clinical application.

Journal of Nanotheranostics doi: 10.3390/jnt7010005

Authors: Alexander Shao-Rong Pang Zi Qiang Glen Liau Jacob Yoong-Leong Oh Dinesh Kumar Srinivasan

In the original publication [...]

Journal of Nanotheranostics doi: 10.3390/jnt7010004

Authors: Marcia Bastos Convento Fernanda Teixeira Borges

Acute and chronic kidney diseases remain significant challenges in regenerative medicine, with few therapies capable of reversing tissue injury or preventing progression. Bone marrow mesenchymal stem cell-derived exosomes (BM-MSC-Exos) are nanosized vesicles (30–150 nm) that have emerged as multifunctional nanotheranostic platforms, combining targeted therapeutic activity with imaging-enabled monitoring. In renal pathophysiology, BM-MSC-Exos exert anti-inflammatory, anti-fibrotic, angiogenic, and pro-regenerative effects. These actions are mediated by microRNAs, messenger RNAs, mitochondrial regulators, and bioactive proteins that modulate epithelial repair and immune responses. Recent bioengineering advances enable more precise BM-MSC-Exos design, including enrichment with synthetic RNAs or gene-editing components and membrane functionalization to enhance kidney tropism. In parallel, fluorescence, bioluminescence, and nanoparticle-based approaches support in vivo tracking. These tools allow real-time assessment of biodistribution and tubular uptake, strengthening evidence for target engagement. This review synthesizes current knowledge on BM-MSC-Exos in renal repair. We summarize contemporary strategies for cargo and surface engineering, outline imaging methodologies for in vivo tracking, and discuss how administration routes influence renal targeting. We also provide an updated overview of clinical trials evaluating exosomes as therapeutic agents or biomarkers in nephrology. Collectively, engineered BM-MSC-Exos represent a promising and increasingly sophisticated platform for precision-guided kidney therapy, supported by monitoring tools that facilitate preclinical evaluation of biodistribution and efficacy.

Journal of Nanotheranostics doi: 10.3390/jnt7010003

Authors: Cristian F. Rodríguez Paula Guzmán-Sastoque Juan Esteban Rodríguez Wilman Sanchez-Hernandez Juan C. Cruz

Metal–organic frameworks (MOFs) are among the most structurally diverse classes of crystalline nanomaterials, offering exceptional tunability, porosity, and chemical modularity. These characteristics have positioned MOFs as promising platforms for nanomedicine, bioimaging, and integrated nanotheranostic applications. However, the rational design of MOFs that satisfy stringent biomedical requirements, including high drug loading capacity, controlled and stimuli responsive release, selective targeting, physiological stability, biodegradability, and multimodal imaging capability, remains challenging due to the vast combinatorial design space and the complex interplay between physicochemical properties and biological responses. The objective of this review is to critically examine recent advances in artificial intelligence approaches based on Transformer architectures for the design and optimization of MOFs aimed at next-generation nanotheranostics. In contrast to prior reviews that broadly survey machine learning methods for MOF research, this article focuses specifically on Transformer-based models and their ability to capture long-range, hierarchical, and multiscale relationships governing MOF structure, chemistry, and functional behavior. We review state-of-the-art models, including MOFormer, MOFNet, MOFTransformer, and Uni MOF, and discuss graph-based and sequence-based representations used to encode MOF topology and composition. This review highlights how Transformer-based models enable predictive assessment of properties directly relevant to nanotheranostic performance, such as adsorption energetics, framework stability, diffusion pathways, pore accessibility, and surface functionality. By explicitly linking these predictive capabilities to drug delivery efficiency, imaging performance, targeted therapeutic action, and combined diagnostic and therapeutic applications, this work delineates the specific contribution of Transformer-based artificial intelligence to biomedical translation. Finally, we discuss emerging opportunities and remaining challenges, including generative Transformer models for inverse MOF design, self-supervised learning on hybrid experimental and computational datasets, and integration with autonomous synthesis and screening workflows. By defining the scope, novelty, and contribution of Transformer-based design strategies, this review provides a focused roadmap for accelerating the development of MOF-based platforms for next-generation nanotheranostics.

Journal of Nanotheranostics doi: 10.3390/jnt7010002

Authors: Tozivepi Aaron Munyayi Anine Crous Heidi Abrahamse

This study presents a multifunctional theranostic platform based on anisotropic gold nanostars (AuNSs) functionalized with 2-thiouracil (2-TU) for cancer diagnostics and photothermal therapy (PTT). The unique plasmonic properties of AuNSs, combined with the anticancer and photothermal potential of 2-TU, were harnessed to create a system capable of simultaneous colorimetric biosensing and therapeutic action. Under dual-wavelength irradiation (660 nm and 525 nm), the AuNSs–2-TU conjugate demonstrated enhanced photothermal conversion efficiency, selective cancer cell targeting, and signal amplification, resulting in a significant reduction in the IC50 for MCF-7 breast cancer cells. The system exhibited minimal cytotoxicity to normal fibroblasts (WS1), ensuring therapeutic precision. Compared to conventional spherical gold nanoparticles, this platform provides superior multifunctionality, including real-time biosensing with simple, naked-eye colorimetric readouts. These results highlight the potential of the AuNSs–2-TU conjugate as an innovative, minimally invasive nanotheranostic platform suitable for integrated cancer detection and treatment, particularly in resource-constrained settings.

Journal of Nanotheranostics doi: 10.3390/jnt7010001

Authors: Sumsuddin Chowdhury Aman Kumar Preeti Patel Balak Das Kurmi Shweta Jain Banty Kumar Ankur Vaidya

Diabetic wounds remain chronically non-healing due to impaired angiogenesis, persistent inflammation, and defective extracellular matrix remodelling. In recent years, stem cell-derived exosomes have emerged as a potent cell-free regenerative strategy capable of recapitulating the therapeutic benefits of mesenchymal stem cells while avoiding risks associated with direct cell transplantation. This review critically evaluates the preclinical evidence supporting the use of exosomes derived from adipose tissue, bone marrow, umbilical cord, and induced pluripotent stem cells for diabetic wound repair. These exosomes deliver bioactive cargos such as microRNAs, proteins, lipids, and cytokines that modulate key signalling pathways, including Phosphatidylinositol 3-kinase/Protein kinase (PI3K/Akt), Nuclear factor kappa B (NF-κB), Mitogen-activated protein kinase (MAPK), Transforming growth factor-beta (TGF-β/Smad), and Hypoxia inducible factor-1α/Vascular endothelial growth factor (HIF-1α/VEGF), thereby promoting angiogenesis, accelerating fibroblast and keratinocyte proliferation, facilitating re-epithelialization, and restoring immune balance through M2 macrophage polarization. A central focus of this review is the recent advances in exosome-based delivery systems, including hydrogels, microneedles, 3D scaffolds, and decellularized extracellular matrix composites, which significantly enhance exosome stability, retention, and targeted release at wound sites. Comparative insights between stem cell therapy and exosome therapy highlight the superior safety, scalability, and regulatory advantages of exosome-based approaches. We also summarize progress in exosome engineering, manufacturing, quality control, and ongoing clinical investigations, along with challenges related to standardization, dosage, and translational readiness. Collectively, this review provides a comprehensive mechanistic and translational framework that positions stem cell-derived exosomes as a next-generation, cell-free regenerative strategy with the potential to overcome current therapeutic limitations and redefine clinical management of diabetic wound healing.

Journal of Nanotheranostics doi: 10.3390/jnt6040035

Authors: Xinhao Jin Qi Sun

Cancer remains a severe global health threat, with traditional therapies often plagued by limited efficacy and significant side effects. The emergence of nanotechnology, particularly metal-doped nanomaterials, offers a promising avenue for integrating diagnostic and therapeutic functions into a single platform, enabling a theranostic approach to oncology. This article explores the design and application of various metal-doped nanosystems, including gadolinium-doped selenium molybdenum nanosheets for magnetic resonance/photoacoustic dual-mode imaging and photothermal therapy, and metal-doped hollow mesoporous silica nanoparticles that leverage the tumor’s acidic microenvironment to release ions for catalytic generation of reactive oxygen species. Despite their promise, the limited enzyme-like activity of some nanozymes, insufficient endogenous hydrogen peroxide in tumors, and the tumor microenvironment’s defensive mechanisms, such as high glutathione levels, can restrict therapeutic efficacy. Looking forward, the outlook for the field is contingent upon advancing material engineering strategies. Future research should prioritize the development of intelligent, multifunctional nanoplatforms that can dynamically respond to and remodel the tumor microenvironment. Innovations in surface modification for enhanced targeting, alongside rigorous preclinical studies focused on safety and standardized manufacturing, are crucial for bridging the gap between laboratory research and clinical application, ultimately paving the way for personalized cancer medicine.

Journal of Nanotheranostics doi: 10.3390/jnt6040034

Authors: Tai L. Guo Ayushi Bhagat Daniel J. Guo

Obesity and type 2 diabetes are closely linked and often referred to as diabesity. Therapies of diabesity include improving intestinal health and reducing intake of fat and sugars. Diagnosis of diabesity-related metabolic disorders would involve monitoring of glucose and other factors. Nanocellulose, also known as cellulose nanomaterials, is emerging as a potential material for various applications. It has unique properties, such as high surface area, biodegradable, biocompatibility and tunable surface chemistry. In this review, we initially provided a brief description of differently produced nanocellulose and their potential applications in different areas, including therapeutics and diagnostics, by focusing on obesity and diabetes. Then, the uptake, absorption, distribution, metabolism and excretion of nanocellulose were discussed. Further, the mechanisms of nanocellulose in modulating diabesity were summarized by emphasizing the role of gut microbiota. Finally, we discussed gut microbiota-related health effects of nanocellulose, both beneficial and detrimental. It was found that the interactions between nanocellulose and gut were complex, with alterations of microbial composition, metabolic activity, and the immune functions both locally and systemically. There seemed to be many beneficial changes following short-term exposure to nanocellulose (e.g., increased beneficial bacteria and decreased pathogenic ones); however, some of these effects were no longer seen after long-term consumption. Importantly, long-term nanocellulose consumption may be associated with certain detrimental health effects, e.g., malnutrition and its associated neurotoxicity, although additional studies are needed to substantiate such health implications. This information is critical for developing safe and effective nanocellulose derivatives that can be applied in food and medicine as well as to harness the benefits of the gut microbiota.

Journal of Nanotheranostics doi: 10.3390/jnt6040033

Authors: Renée Onnainty Gladys E. Granero

Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to be a leading cause of death from a single infectious agent worldwide. Conventional antibiotic therapies face significant limitations, including multidrug resistance, poor treatment adherence, limited penetration into granulomas, and systemic toxicity. Recent advances in nanomedicine have paved the way for nanotheranostic approaches that integrate therapeutic, diagnostic, and preventive functions into a single platform. Nanotheranostic systems enable targeted drug delivery to infected macrophages and granulomatous lesions, real-time imaging for disease monitoring, and controlled, stimuli-responsive release of antitubercular agents. These platforms can be engineered to modulate host immune responses through host-directed therapies (HDTs), including the induction of autophagy, regulation of apoptosis, and macrophage polarization toward the bactericidal M1 phenotype. Additionally, nanocarriers can co-deliver antibiotics, immunomodulators, or photosensitizers to enhance intracellular bacterial clearance while minimizing off-target toxicity. The review also discusses the potential of nanotechnology to improve TB prevention by enhancing vaccine efficacy, stability, and targeted delivery of immunogens such as BCG and novel subunit vaccines. Key nanoplatforms, including polymeric, lipid-based, metallic, and hybrid nanoparticles, are highlighted, along with design principles for optimizing biocompatibility, multifunctionality, and clinical translatability. Collectively, nanotheranostic strategies represent a transformative approach to TB management, bridging diagnosis, therapy, and prevention in a single, adaptable platform to address the unmet needs of this global health challenge.

Journal of Nanotheranostics doi: 10.3390/jnt6040032

Authors: Panangattukara Prabhakaran Praveen Kumar

Magnetic Particle Imaging (MPI) is a cutting-edge noninvasive imaging technique that offers high sensitivity, quantitative accuracy, and operates without the need for ionizing radiation compared to other imaging techniques. Utilizing superparamagnetic iron oxide nanoparticles (SPIONs) as tracers, MPI enables direct and precise visualization of target sites with no limitation on imaging depth. Unlike magnetic resonance imaging (MRI), which relies on uniform magnetic fields to produce anatomical images, MPI enables direct, background-free visualization and quantification of SPIONS within living organisms. This article provides an in-depth overview of MPI’s applications in tracking tumor development and supporting cancer therapy. The distinct physical principles that underpin MPI, including its ability to produce high-contrast images devoid of background tissue interference, facilitating accurate tumor identification and real-time monitoring of treatment outcomes, are outlined. The review outlines MPI’s advantages over conventional imaging techniques in terms of sensitivity and resolution, and examines its capabilities in visualizing tumor vasculature, tracking cellular movement, evaluating inflammation, and conducting magnetic hyperthermia treatments. Recent progress in tracer optimization and magnetic navigation has expanded MPI’s potential for targeted drug delivery, along with deep machine learning procedures for MPI applications. Additionally, considerations around safety and the feasibility of clinical implementation are also discussed in the present review. Overall, MPI is positioned as a promising tool in advancing cancer diagnostics, personalized therapy assessment, and noninvasive treatment strategies.

Journal of Nanotheranostics doi: 10.3390/jnt6040031

Authors: Poornima Ramburrun Theresa P. K. Varughese Yahya E. Choonara

Periodontitis is a chronic, multifactorial inflammatory disease characterized by the progressive destruction of the tooth-supporting structures. Conventional therapeutic approaches, including mechanical debridement and systemic antibiotics, often fall short in achieving complete bacterial eradication or tissue regeneration, particularly in deep periodontal pockets. Nanotheranostics—an integrated platform combining diagnostics and therapeutics within a single nanosystem—holds promise in advancing periodontal care through targeted delivery, real-time disease monitoring, and site-specific therapy. This narrative review examines the potential of various nanomaterials for building nanotheranostic systems to overcome current clinical limitations, including non-specific drug delivery, insufficient treatment monitoring, and delayed intervention, and their functionalization and responsiveness to the periodontal microenvironment are discussed. Their application in targeted antimicrobial, anti-inflammatory, and regenerative therapy is discussed in terms of real-time monitoring of disease biomarkers and pathogenic organisms. Although nanoparticle-based therapeutics have been extensively studied in periodontitis, the integration of diagnostic elements remains underdeveloped. This review identifies key translational gaps, evaluates emerging dual-function platforms, and discusses challenges related to biocompatibility, scalability, and regulatory approval. In particular, inorganic nanomaterials exhibit potential for theranostic functions such as antimicrobial activity, biofilm disruption, immunomodulation, tissue regeneration, and biosensing of microbial and inflammatory biomarkers. Finally, we propose future directions to advance nanotheranostic research toward clinical translation. By consolidating the current evidence base, this review advocates for the development of smart, responsive nanotheranostic platforms as a foundation for personalized, minimally invasive, and precision-guided periodontal care.

Journal of Nanotheranostics doi: 10.3390/jnt6040030

Authors: Marco Chávez-Tinoco Bruno Solis-Cruz Edgar R. López-Mena Karla S. García-Salazar Daniel Hernández-Patlán Jorge L. Mejía-Méndez

Viral diseases remain a persistent threat to global health, agriculture, and biodiversity, as demonstrated by recent pandemics. The high mutation rates, diversity, and intricate replication mechanisms within a host can often challenge conventional detection and therapeutic approaches. The emergence of novel viruses underscores the critical importance of innovative and multidisciplinary strategies to outpace these diseases. In this context, nanotechnology has emerged as a transformative frontier, offering unique tools to address the limitations of traditional virology. This review examines the latest nanotechnological innovations designed to combat viral diseases. Like the development of advanced nanoplatforms, metallic and polymeric nanostructures, and carbon-based materials, and evaluating their roles in viral theranostics. This article provides critical biomedical insights into the function and relationship of nanomaterials, mechanisms of action, and their interaction with biological systems. This work aims to provide a valuable resource for guiding future research toward the clinical translation of nanomaterial-based strategies for the prevention, diagnosis, and treatment of viral infections.

Journal of Nanotheranostics doi: 10.3390/jnt6040029

Authors: Victor Akpe Ian E. Cock

The integration of nanotheranostics into cancer treatment represents a transformative shift in oncology, combining precision diagnostics with targeted therapeutic interventions. This manuscript explores the advancements in nanotechnology-driven cancer therapies, highlighting the role of engineered nanoparticles, such as liposomes, dendrimers, polymeric micelles, and virus-like particles, in enhancing drug delivery, real-time imaging, and tumor-specific targeting. Additionally, emerging therapies, including immunotherapy, gene editing, and chromophore-assisted light inactivation (CALI), are discussed in the context of personalized medicine. The convergence of these strategies is poised to redefine cancer treatment paradigms, improving therapeutic efficacy while minimizing systemic toxicity. This review outlines the key challenges, current limitations, and future directions in nanotheranostic applications, emphasizing the need for interdisciplinary collaboration to optimize their clinical translation.

Journal of Nanotheranostics doi: 10.3390/jnt6040028

Authors: Kay Hadrick Panangattukara Prabhakaran Praveen Kumar Taeho Kim

The immune system is crucial in protecting against disease, but it can also contribute to chronic illnesses when it malfunctions, with different conditions involving either inflammation or immune suppression. Current treatments often fall short due to limited effectiveness and side effects. Nanomedicine, particularly cerium oxide nanoparticles (nanoceria), offers promising potential due to its unique therapeutic properties and role in modulating macrophages. Nanoceria (<5 nm) possess the catalytic ability to mimic natural enzymes such as superoxide dismutase, peroxidase, and catalase, enabling effective scavenging of reactive oxygen species (ROS), which play a central role in the pathogenesis of chronic inflammation and cancer. This review comprehensively summarizes the current advances in the application of nanoceria for inflammatory and anti-inflammatory therapy, including their modulatory effects on immune cell activation, cytokine production, and resolution of inflammatory responses. We discuss the mechanisms underlying their immunomodulatory actions in various disease contexts, such as rheumatoid arthritis, women’s health conditions (e.g., endometriosis), wound healing, and cancer. Additionally, the review highlights biocompatibility, therapeutic efficacy, adaptability in imaging (theranostics), and challenges in translating nanoceria-based therapies into clinical practice. The multifunctionality of nanoceria positions them as innovative candidates for next-generation immunotherapy aimed at efficiently controlling inflammation and promoting tissue repair.

Journal of Nanotheranostics doi: 10.3390/jnt6040027

Authors: María Jimena Salgueiro Marcela Zubillaga

The convergence of nanotechnology with nuclear medicine has led to the development of theranostic nanoplatforms that combine targeted imaging and therapy within a single system. This review provides a critical and updated synthesis of the current state of nanoplatform-based theranostics, with a particular focus on their application in oncology. We explore multifunctional nanocarriers that integrate diagnostic radionuclides for SPECT/PET imaging with therapeutic radioisotopes (α-, β-, or Auger emitters), chemotherapeutics, and biological targeting ligands. We highlight advances in nanomaterial engineering—such as hybrid architectures, surface functionalization, and stimuli-responsive designs—that improve tumor targeting, biodistribution, and therapeutic outcomes. Emphasis is placed on translational challenges including pharmacokinetics, toxicity, regulatory pathways, and GMP-compliant manufacturing. The article closes with a forward-looking perspective on how theranostic nanoplatforms could reshape the future of personalized oncology through precision-targeted diagnostics and radiotherapy.

Journal of Nanotheranostics doi: 10.3390/jnt6040026

Authors: André Felipe Oliveira Isabela Barreto da Costa Januário Meireles Maria Angela Barros Correia Menezes Klaus Krambrock Edésia Martins Barros de Sousa

Among the many nanomaterials studied for biomedical uses, silica and gold nanoparticles have gained significant attention because of their unique physical and chemical properties and their compatibility with living tissues. Mesoporous silica nanoparticles (MSNs) have great stability and a large surface area, while gold nanoparticles (AuNPs) display remarkable optical features. Both types of nanoparticles have been widely researched for their individual roles in drug delivery, imaging, biosensing, and therapy. When combined with gadolinium (Gd), a common contrast agent, these nanostructures provide improved imaging due to gadolinium’s strong paramagnetic properties. This study focuses on incorporating gold nanoparticles and gadolinium into a silica matrix to develop a theranostic system. Various analytical techniques were used to characterize the nanocomposites, including infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-Vis), thermogravimetric analysis (TGA), nitrogen adsorption, scanning electron microscopy (SEM), dynamic light scattering (DLS), X-ray fluorescence (XRF), X-ray diffraction (XRD), vibrating sample magnetometry (VSM), and neutron activation analysis (NAA). Techniques like XRF mapping, XANES, nitrogen adsorption, SEM, and VSM were crucial in confirming the presence of gadolinium and gold within the silica network. VSM and EPR analyses confirmed the attenuation of the saturation magnetization for all nanocomposites. This validates their potential for biomedical applications in diagnostics. Moreover, activating gold nanoparticles in a nuclear reactor generated a promising radioisotope for cancer treatment. These results indicate the potential of using a theranostic nanoplatform that employs mesoporous silica as a carrier, gold nanoparticles for radioisotopes, and gadolinium for imaging purposes.

Journal of Nanotheranostics doi: 10.3390/jnt6030025

Authors: Nutan Shukla Aayushi Chanderiya Ratnesh Das Elizaveta A. Mukhanova Alexander V. Soldatov Sabrina Belbekhouche

AuQDs (Au quantum dots) are ultrasmall nanostructures that combine the size-tunable fluorescence and photostability of semiconductor quantum dots with the chemical stability, low toxicity, and versatile surface chemistry of gold nanoparticles. This unique combination endows AuQDs with exceptional biocompatibility and multifunctionality, making them ideal for biomedical applications such as cellular imaging, real-time tracking, targeted drug delivery, diagnostics, therapeutic monitoring, and biosensing. Various synthesis methods—including chemical reduction, hydrothermal, laser ablation, and microwave-assisted techniques—allow for precise control over size and surface properties, optimizing fluorescence and electronic behavior for high-resolution imaging and sensitive detection. Compared to traditional quantum dots, AuQDs offer enhanced safety and biocompatibility, while surpassing larger gold nanoparticles by enabling fluorescence-based imaging. Their surfaces can be functionalized with diverse ligands for targeted delivery and specific biological interactions. In summary, AuQDs are multifunctional nanoprobes that combine superior optical properties, chemical stability, and biocompatibility, making them powerful tools for advanced biomedical diagnostics, therapy, and biosensing.

Journal of Nanotheranostics doi: 10.3390/jnt6030024

Authors: Hossein Omidian Erma J. Gill Luigi X. Cubeddu

Nanotheranostics combines therapeutic and diagnostic functions within multifunctional nanoparticle platforms to enable precision medicine. This review outlines a comprehensive framework for engineering nanotheranostic systems, focusing on core material composition, surface functionalization, and stimuli-responsive drug delivery. Targeting strategies—from ligand-based recognition to biomimetic interfaces—are examined alongside therapeutic modalities such as chemotherapy, photothermal and photodynamic therapies, gene silencing via RNA interference, and radio sensitization. We discuss advanced imaging techniques (fluorescence imaging FI), magnetic resonance imaging (MRI), positron emission tomography (PET), and photoacoustic imaging for real-time tracking and treatment guidance. Key considerations include physicochemical characterization (e.g., article size, surface charge, and morphology), biocompatibility, in-vitro efficacy, and in-vivo biodistribution. We also address challenges such as rapid biological clearance, tumor heterogeneity, and clinical translation, and propose future directions for developing safe, adaptable, and effective nanotheranostic platforms. This review serves as a roadmap for advancing next-generation nano systems in biomedical applications.

Journal of Nanotheranostics doi: 10.3390/jnt6030023

Authors: Phuoc V. Nguyen Darnetty Eka Candra Lina Nha V. Duong Phuong T. H. T. B. Ho Di Ba Huỳnh

Magnaporthe oryzae-induced rice blast remains a critical threat to sustainable rice farming, causing extensive losses in many rice-producing regions worldwide. Due to increasing concerns about pesticide overuse and its impact on the environment and human health, alternative control methods are being actively explored. Nanotechnology has recently gained attention as a potential tool for sustainable disease management. This review summarises current progress in the use of nanomaterials—including metal and biopolymer nanoparticles, nanoemulsions, targeted delivery systems, and biosensors—for the detection and control of rice blast. Studies have reported that nanomaterials can reduce disease severity by up to 70% and improve rice yield by 10–20% under field or greenhouse conditions. The mode of action, effectiveness under field conditions, and possible integration into integrated pest management (IPM) programs are discussed. The selection of literature followed the PRISMA-P framework to ensure a systematic and transparent review process. Challenges such as biosafety, environmental risks, and regulatory issues are also addressed, with emphasis on green synthesis methods and the need for field validation before practical application.

Journal of Nanotheranostics doi: 10.3390/jnt6030022

Authors: Fong-Yu Cheng Boguslaw Tomanek Barbara Blasiak

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive type of pancreatic cancer. PDAC is difficult to diagnose due to a lack of symptoms in early stages, resulting in a survival rate of less than 10%. Moreover, often cancerous tissues cannot be surgically resected due to their deep abdomen location. Therefore, early detection is the essential strategy enabling effective PDAC treatment. Over the past few years, the development of nanomaterials for Magnetic Resonance Imaging (MRI) has expanded and improved imaging quality and diagnostic accuracy. Nanomaterials can be currently designed, manufactured and synthesized with other structures to provide improved diagnosis and advanced therapy. Although MRI equipped with the innovative nanomaterials became a powerful tool for the diagnosis and treatment of patients with various cancers, the detection of PDAC remains challenging. Nevertheless, recent advancements in PDAC theranostics provided progress in the detection and treatment of this challenging type of cancer. Present research in this area is focused on suitable carriers, eliminating delivery barriers, and the development of efficient anti-cancer drugs. Herein we discuss the current applications of iron oxide nanoparticles to the MRI diagnosis and treatment of pancreatic cancer.

Journal of Nanotheranostics doi: 10.3390/jnt6030021

Authors: Abeer Alanazi Alexander Craven Spiridon V. Spirou Maria Jose Santos-Martinez Carlos Medina Oliviero L. Gobbo

Obesity is a chronic disorder associated with serious comorbidities such as diabetes, cardiovascular disease, and cancer. Conventional pharmacological treatments often suffer from limited efficacy, poor selectivity, and undesirable side effects, highlighting the need for more effective alternatives. Nanomedicine offers a promising approach by overcoming these limitations through targeted drug delivery and enhanced therapeutic precision. This review examines key nanotechnological strategies in obesity management, including targeting white adipose tissue (WAT) and the vascular marker prohibitin, promoting WAT browning, and utilizing photothermal therapy and magnetic hyperthermia as nanotheranostic tools. We discuss major nanomedicine platforms—such as liposomes, nanoemulsions, and polymeric nanoparticles—alongside emerging applications in gene nanotherapy and herbal formulations. Potential toxicity concerns are also addressed. In summary, nanomedicine holds substantial potential to revolutionize obesity treatment through targeted, effective, and multifunctional therapeutic strategies.

Journal of Nanotheranostics doi: 10.3390/jnt6030020

Authors: Yue Li Dmitri Simberg

There was an error in the original publication [...]

Journal of Nanotheranostics doi: 10.3390/jnt6030019

Authors: Furqan Choudhary Ubaid Mushtaq Naikoo Amber Rizwan Jasmeet Kaur Malik Z. Abdin Humaira Farooqi

Lung cancer remains one of the main causes of cancer-related death globally and a significant global health concern. There is an urgent need for safer and more effective therapeutic alternatives despite notable progress in therapy; issues such as drug resistance, side effects, metastasis, and recurrence still affect patient outcome and quality of life. The aim of this review is to examine recent developments in the application of herbal-drug-loaded nanoparticles as a new strategy for treating lung cancer. A thorough examination of different drug delivery systems based on nanoparticles is provided, highlighting their function in improving the solubility, bioavailability, and targeted delivery of herbal compounds. In addition, the review evaluates the biomarkers used for targeted therapy and examines how new personalised treatment approaches like wearable electronic patches, robotics-assisted interventions, smartphone-enabled therapies, AI-driven diagnostics, and lung-on-a-chip technologies can be integrated to improve the accuracy and effectiveness of lung cancer treatment. In conclusion, the combination of personalised medicine and nanotechnology may lead to revolutionary changes in lung cancer treatment in the future.

Journal of Nanotheranostics doi: 10.3390/jnt6030018

Authors: Razvan Septimiu Zdrehus Teodora Mocan Lavinia Ioana Sabau Cristian Tudor Matea Alexandru-Flaviu Tabaran Teodora Pop Cristian Delcea Ofelia Mosteanu Lucian Mocan

Background and Aim: Colorectal cancer remains a leading cause of cancer-related mortality, with growing interest in nanotechnology-driven immunotherapeutics. Gold nanoparticles (AuNPs) offer a promising platform due to their biocompatibility, functional versatility, and immunomodulatory potential. Carcinoembryonic antigens (CEAs), highly expressed in colorectal tumors, provide an ideal target for antigen-specific immune activation. The aim of this study is to evaluate the immunogenicity, biodistribution, and therapeutic efficacy of a CEA-functionalized gold nanoparticle (CEA-AuNP) construct in a mouse model of colorectal cancer following oral administration via a customized capsular delivery system. Methods: A 30-day oral administration study was performed in BALB/c mice (n = 30), who received increasing doses of CEA-AuNPs (5–50 mg/kg/day). Histological, hyperspectral imaging, and ELISA-based cytokine analyses were conducted to assess organ integrity, nanoparticle accumulation, and immune modulation. Results: CEA-AuNPs demonstrated a favorable safety profile and dose-dependent accumulation in reticuloendothelial tissues, particularly the spleen and liver. Cytokine profiling revealed enhanced IL-10 responses in the spleen, indicating anti-inflammatory immune modulation, with localized pro-inflammatory signals observed in hepatic tissue at higher doses. No signs of systemic toxicity or significant off-target effects were detected. Conclusions: The oral administration of CEA-AuNPs in healthy mice induced tissue-specific immune responses and exhibited a dose-dependent biodistribution pattern. These results support the further development of CEA-AuNPs as a nanovaccine platform for colorectal cancer immunoprophylaxis.

Journal of Nanotheranostics doi: 10.3390/jnt6030017

Authors: Michael Valceski Anson Tsan Yin O Alice O’Keefe Sarah Vogel Elette Engels Kiarn Roughley Abass Khochaiche Dylan Potter Carolyn Hollis Anatoly Rosenfeld Michael Lerch Stéphanie Corde Moeava Tehei

High-Z nanoparticles (NPs) have the potential to revolutionize cancer radiotherapy by radiosensitising tumours. This is particularly important for radioresistant cancers such as glioblastoma. A newer NP candidate in this area is thulium oxide nanoparticles (TmNPs). However, prior to clinical assessment, ideal NP characteristics, including biocompatibility, biosafety, and preferential uptake in cancer, should be assessed. This in vitro study compares the effects of TmNP treatment, without radiation, on 9L gliosarcoma (9LGS), a well-established glioblastoma cell model, with exposure to Madin Darby Canine Kidney (MDCK) cells, a widely used non-cancerous cell model. The findings demonstrated selective uptake of TmNPs in 9LGS over MDCK following treatment. A biological assessment of toxicity confirmed minimal long-term effects on MDCK, whilst TmNPs were observed to induce some notable cell death in 9LGS. Excessive TmNP uptake in 9LGS over time was observed to induce cell vacuolisation, which resulted in cell death via necrosis. It was concluded that this was the explanation for the underlying mechanisms of TmNP toxicity in cancer cells. This study was therefore able to demonstrate not only that TmNPs are a biocompatible, cancer-selective candidate for radiosensitiser usage, but further provided a theory to explain its mechanisms of cancer cell toxicity.

Journal of Nanotheranostics doi: 10.3390/jnt6030016

Authors: Yue Li Dmitri Simberg

Superparamagnetic iron oxide (SPIO) nanoparticles are a promising platform for drug delivery and magnetic resonance imaging (MRI). However, complement activation and immune recognition remain major barriers to their clinical translation. Previously, we reported that dextran-coated SPIO nanoworms (NWs) trigger potent complement activation and infusion reactions. Here, we systematically map the temporal sequence of immune events following SPIO NW administration, including C3 opsonization, granulocyte uptake, and cytokine release. In both in vitro and in vivo models, C3 deposition occurred rapidly, peaking at approximately 5 min post-incubation or post-injection. Higher Fe/plasma ratios led to reduced C3 deposition per particle, although the absolute amount of C3 bound was greater in vivo than in vitro. Notably, C3 dissociation from the particle surface exhibited a consistent half-life of ~14 min, independent of the NW injected dose and circulation time. Immune uptake by blood granulocytes was delayed relative to opsonization, becoming prominent only at 60 min post-injection. Further, cytokine release, measured by plasma IL-6 levels, displayed an even slower profile, with peak expression at 6 h post-injection. Together, these results reveal a distinct sequential immune response to SPIO NWs: rapid C3 opsonization, delayed cellular uptake, and late cytokine response. Understanding these dynamics provides a basis for developing strategies to inhibit complement activation and improve the hemocompatibility of SPIO-based theranostic agents.

Journal of Nanotheranostics doi: 10.3390/jnt6020015

Authors: Seyed Moein Moghimi Simó Schwartz

Broadly speaking, theranostics is not just a combination of imaging and therapy [...]

Journal of Nanotheranostics doi: 10.3390/jnt6020014

Authors: Esther Ghanem

Exhaled breath condensate (EBC) has gained attention as a diagnostic gateway for lung diseases, brain–gut microbiota dysbiosis, and biobanking. Due to its non-invasive and fast collection method, EBC collection is not under temporal or volume limitations. Nonetheless, conventional EBC screening methods are complex and require high operational costs and expertise. Thus, the advent of nanotechnology has introduced efforts for using nanosensors as EBC analyzers. Over the past decade, multiple EBC-based studies reported the successful use of functionalized nanosensors to trace oxidative stress, tissue damage, and respiratory diseases. The EBC signature includes biomarkers such as gases (H2O2 and VOCs), cations (polyamines), fatty acids, cytokines, and aldehydes, in addition to traces of drugs and antibiotics. A common feature of nanosensors is their ability to amplify signals and rapidly detect EBC analytes with high sensitivity and specificity. Based on the collected data, standardizing the collection protocol and read-out methods across laboratories is essential for optimal data comparability. Larger cohorts should be considered to ensure a reliable reproducibility of the reported outputs. Future research directions should employ EBC-based nanosensors to unravel the unexplored omics of lung diseases, especially those linked to the brain–gut microbiota that might influence airway immunity.

Journal of Nanotheranostics doi: 10.3390/jnt6020013

Authors: Abhishu Chand Kyoungtae Kim

Metal–organic frameworks (MOFs) along with quantum dots (QDs) are independent structures that have garnered attention in the biomedical field due to their unique chemo-physical characteristics. MOFs are highly porous and tunable structures, while QDs are nanomaterials with excellent optical and fluorescent properties which make these potent diagnostic tools for sensing, detection, and therapeutics. Despite their potential, both materials have their shortcomings in terms of long-term stability and toxicity. However, the integration of these two materials to form QD–MOF hybrid systems has emerged to combine their strengths and overcome their limitations, introducing new possibilities for advanced therapeutic applications. In this mini review, we explore the evolution of the QD–MOF hybrid systems, focusing on their functional properties and applications in sensing, drug delivery and cancer therapy. Furthermore, we discuss the current implementation of this system and its future possibilities, exhibiting the novel impacts of the QD–MOF hybrids in biomedical research and clinical applications.

Journal of Nanotheranostics doi: 10.3390/jnt6020012

Authors: María Jimena Salgueiro Marcela Analia Moretton Vanina Medina Diego Chiappetta Marcela Zubillaga

Pharmacoscintigraphy has emerged as an essential tool in the research and development of nanomedicines, particularly in the field of nanotheranostics. By enabling the real-time, non-invasive tracking of their biodistribution, pharmacokinetics, and therapeutic efficacy, these imaging techniques provide invaluable insights that drive the optimization of nanomedicine formulations. The integration of gamma scintigraphy, SPECT, and PET imaging has significantly enhanced our understanding of nanocarrier behavior, supporting their clinical translation by ensuring precise targeting, minimizing off-target effects, and improving therapeutic outcomes. Future advancements in hybrid imaging modalities, novel radionuclide tracers, and personalized imaging-guided therapies will further expand the impact of pharmacoscintigraphy in nanomedicine. Additionally, the increasing recognition of imaging-based validation in regulatory approval processes underscores the growing importance of these techniques in drug development. As nanotheranostics continues to evolve, radionuclide imaging will remain a pivotal component in their preclinical and clinical evaluation, facilitating safer and more effective precision medicine approaches.

Journal of Nanotheranostics doi: 10.3390/jnt6020011

Authors: Danielle Teixeira Freire Júlio Abreu Miranda Douglas Dourado Éverton do Nascimento Alencar

Theranostic nanoparticles integrate diagnostic and therapeutic potential, representing a promising approach in precision medicine. Accordingly, numerous inventions have been patented to protect novel formulations and methods. This review examines the evolution of patented theranostic nanoparticles, focusing on organic nanosystems, particularly polymeric and lipid nanoparticles, to assess their development, technological advances, and patentability. A scoping review approach was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines in the World Intellectual Property Organization (WIPO) and European Patent Office (EPO) database. The search included patents filed within the last ten years (2014–2024) that specifically claimed organic and/or hybrid theranostic nanoparticles. Data extraction focused on nanoparticle composition, synthesis methods, functionalization strategies, and theranostic applications. The search identified 130 patents, of which 13 met the inclusion criteria. These patents were primarily filed by inventors from the United States, Canada, Great Britain, Italy, and China. Polymeric nanoparticles were frequently engineered for targeted drug delivery and imaging, utilizing hyperbranched polyesters, sulfated polymers, or chitosan-based formulations. Lipid nanoparticles were often hybridized with inorganic nanomaterials or magnetic nanostructures to enhance their theranostic potential. While most patents detailed synthesis methods and physicochemical characterizations, only a few provided comprehensive preclinical validation, limiting their demonstrated efficacy. The analysis of recent patents highlights significant advances in the design and application of theranostic nanoparticles. However, a notable gap remains in validating these nanosystems for clinical translation. Future efforts should emphasize robust preclinical data, including in vitro and in vivo assessments, to enhance patent quality and applicability to substantiate the claimed theranostic capabilities.

Journal of Nanotheranostics doi: 10.3390/jnt6020010

Authors: Paula Guzmán-Sastoque Cristian F. Rodríguez María Camila Monsalve Stiven Castellanos Andrés Manrique-Moreno Luis H. Reyes Juan C. Cruz

Nanotheranostics—where nanoscale materials serve both diagnostic and therapeutic functions—are rapidly transforming gene therapy by tackling critical delivery challenges. This review explores the design and engineering of various nanoparticle systems (lipid-based, polymeric, inorganic, and hybrid) to enhance stability, targeting, and endosomal escape of genetic payloads. We discuss how real-time imaging capabilities integrated into these platforms enable precise localization and controlled release of genes, improving treatment efficacy while reducing off-target effects. Key strategies to overcome delivery barriers (such as proton sponge effect and photothermal disruption) and to achieve nuclear localization are highlighted, along with recent advances in stimuli-responsive systems that facilitate spatiotemporal control of gene expression. Clinical trials and preclinical studies demonstrate the expanding role of nanotheranostics in managing cancer, inherited disorders, and cardiovascular and neurological diseases. We further address regulatory and manufacturing hurdles that must be overcome for the widespread clinical adoption of nanoparticle-based gene therapies. By synthesizing recent progress and ongoing challenges, this review underscores the transformative potential of nanotheranostics for effective, targeted, and image-guided gene delivery.

Journal of Nanotheranostics doi: 10.3390/jnt6020009

Authors: Dana Mohammed AlQurashi Tayf Fahad AlQurashi Raneia Idrees Alam Sumera Shaikh Mariam Abdulaziz M. Tarkistani

Antibiotic resistance poses a significant global health challenge, undermining the effectiveness of conventional treatments and increasing mortality rates worldwide. Factors such as the overuse and misuse of antibiotics in healthcare and agriculture, along with poor infection control practices, have accelerated the emergence of resistant bacterial strains. The stagnation in the development of new antibiotics, compounded by economic and biological challenges, has necessitated alternative approaches to combat resistant infections. Nanotechnology provides a promising solution using nanoparticles (NPs), which combat bacteria through mechanisms like membrane disruption and reactive oxygen species (ROS) generation. Metal-based nanoparticles such as silver and zinc oxide possess intrinsic antimicrobial properties, while polymer- and carbon-based nanoparticles enhance drug delivery and biofilm penetration. Unlike conventional antibiotics, nanoparticles operate through multi-mechanistic pathways, reducing the likelihood of resistance development and improving treatment efficacy. This review aims to provide an updated, in-depth look at recent advances in nanoparticle research targeting antibiotic resistance, discussing different types of nanoparticles, mechanisms of action, and current challenges and opportunities. By exploring the evolving role of nanotechnology in addressing this crisis, this review intends to highlight the potential for nanoparticles to transform the treatment landscape for resistant bacterial infections and inspire further research into these innovative solutions.

Journal of Nanotheranostics doi: 10.3390/jnt6010008

Authors: Márcia Célia Pacheco Fialho Maria Alice de Oliveira Marina Guimarães Carvalho Machado Carlos Marchiorio Lacerda Vanessa Carla Furtado Mosqueira

Photodynamic and photothermal therapies with IR780 have gained exponential interest, and their photophysical properties have demonstrated promise for use in antitumor and antimicrobial chemotherapy. IR780 and its derivatives are valuable in labeling nanostructures with different chemical compositions for in vitro and in vivo fluorescence monitoring studies in the near-infrared (NIR) spectrum. The current literature is abundant on this topic, particularly with applications in the treatment of different types of cancer using laser illumination to produce photodynamic (PDT), photothermal (PTT), and, more recently, sonodynamic therapy (SDT) approaches for cell death. This review aims to update the state of the art concerning IR780 photosensitizer as a theranostic agent for PDT, PTT, SDT, and photoacoustic (PA) effects, and fluorescence imaging monitoring associated with different types of nanocarriers. The literature update concerns a period from 2017 to 2024, considering, more specifically, the in vivo effects found in preclinical experiments. Some aspects of the labeling stability of nanostructured systems will be discussed based on the evidence of IR780 leakage from the nanocarrier and its consequences for the reliable analysis of biological data.

Journal of Nanotheranostics doi: 10.3390/jnt6010007

Authors: Sourav De Sabyasachi Banerjee Gourab Dey Subhasis Banerjee S.K. Ashok Kumar

A very aggressive and deadly brain cancer, glioblastoma multiforme (GBM) poses formidable obstacles to effective therapy. Despite advancements in conventional therapies like surgery, chemotherapy, and radiation therapy, the prognosis for GBM patients remains poor, with limited survival outcomes. Nanotechnology is gaining popularity as a promising platform for managing GBM, offering targeted drug delivery, improved therapeutic efficacy, and reduced systemic toxicity. This review offers a comprehensive analysis of the current therapeutic approach for GBM using nanotechnology-based interventions. This study explored various nanocarrier (NC) systems like polymeric nanoparticles, liposomes, dendrimers, polymeric micelles, and mesoporous silica nanoparticles for improved precision as well as efficacy in encapsulating and delivering therapeutic agents to GBM tumors. Methods for improving drug delivery into GBM cells are described in this study, including novel delivery modalities such as convection-enhanced delivery, intranasal administration, magnetic hyperthermia, peptide-guided nanoparticles, and immune liposomes. It also explores the influence of diabetes and obesity on GBM prognosis and survival rates, suggesting that managing glucose levels and using metformin may improve patient outcomes. The discussion focuses on the advancements in nanotechnology-enabled GBM therapy, highlighting the challenges and opportunities in implementing these promising technologies in clinical practice. The study highlights the potential of nanotechnology and metabolic modulation in transforming GBM treatment strategies. To further understand how these factors impact GBM patients and develop innovative nanotechnology-based treatments for GBM and diabetes mellitus, more study is necessary.

Journal of Nanotheranostics doi: 10.3390/jnt6010006

Authors: Georgia Savvidou Ellas Spyratou Maria-Eleni Zachou Efstathios P. Efstathopoulos

Nanomedicine is emerging as a groundbreaking strategy for the management of the neuro-visual symptoms of neuroinflammatory and neurodegenerative diseases. This innovative field of study leverages nanoscale materials and technologies to improve drug delivery, enabling targeted treatments to reach the affected ocular tissues. By facilitating the transport of therapeutic agents across the blood–retinal barrier and boosting their bioavailability, nanomedicine holds the potential to significantly mitigate the symptoms of conditions such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), etc. This review summarizes the latest developments in nanomedicine applications for the management of these ocular conditions, highlighting their capacity to foster more effective disease diagnosis and treatment.

Journal of Nanotheranostics doi: 10.3390/jnt6010005

Authors: Rawan Salami Ronit Lavi Yifat Harel Esthy Levy Jean Paul Lellouche Svetlana Gelperina Rachel Persky

This research describes the development and thorough characterization of a novel, versatile, and biocompatible hybrid nanocarrier of the NO-releasing agent NOC-18, with a specific focus on optimizing the purification process. In this study, we focused on the sustained release of NO using biocompatible and diagnostic hybrid magnetic nanoparticles (hMNPs) containing cerium-doped maghemite (CM) NPs, embedded within human serum albumin (HSA) protein. A comprehensive study was conducted using electron paramagnetic resonance (EPR) alongside the Griess assay to evaluate NO release from the chosen NO donor, NOC-18, and to assess the limitations of the molecule under various reaction conditions, identifying the optimal conditions for binding NOC-18 with minimal NO loss. Two types of particles were designed: In-hMNPs, where NOC-18 is encapsulated within the particles, and Out-hMNPs, where NOC-18 is attached onto the surface. Our results demonstrated that In-hMNPs provided a sustained and prolonged release of NO (half-life, 50 h) compared to the rapid release for the Out-hMNPs, likely due to the strong bonds formed with cerium, which helped to stabilize the NO molecules. These results represent a promising approach to designing a dual-function agent that combines contrast properties for tumor MRI with the possibility of increasing the permeability of tumor vasculature. The employment of this dual-function agent in combination with nanotherapeutics could improve the latter’s efficacy by facilitating their access to the tumor.

Journal of Nanotheranostics doi: 10.3390/jnt6010004

Authors: Alexandra A. P. Mansur Herman S. Mansur

Regrettably, despite undeniable advances in cancer diagnosis and therapy, primary brain cancer (or brain cancer) remains one of the deadliest forms of malignant tumors, where glioblastoma (GBM) is known as the most malignant diffuse glioma of astrocytic lineage. Fortunately, to improve this scenario, remarkable progress in nanotechnology has brought new promise and raised expectations in cancer treatment. Nanomedicine, principally an area amalgamating nanotechnology with biology and medicine, has demonstrated a pivotal role, starting with the earliest detection and diagnosis while also offering novel multimodal cancer therapy alternatives. In the vast realm of nanotechnology, nanozymes, a type of nanomaterial with intrinsic enzyme-like activities and characteristics connecting the fields of nanocatalysts, enzymology, and biology, have emerged as powerful nanotools for cancer theranostics. Hence, this fascinating field of research has experienced exponential growth in recent years. As it is virtually impossible to cover all the literature on this broad domain of science in one paper, this review focuses on presenting a multidisciplinary approach, with its content extending from fundamental knowledge of nanozymes and enzyme-mimicking catalysis to the most recent advances in nanozymes for therapy targeting brain cancers. Although we are at the very early stages of research, it can be envisioned that the strategic development of nanozymes in brain cancer theranostics will positively offer disruptive nanoplatforms for future nano-oncology.

Journal of Nanotheranostics doi: 10.3390/jnt6010003

Authors: Cristina Blasco-Navarro Carlos Alonso-Moreno Iván Bravo

Nanotheranostics integrates diagnostic and therapeutic functionalities using nanoscale materials, advancing personalized medicine by enhancing treatment precision and reducing adverse effects. Key materials for nanotheranostics include metallic nanoparticles, quantum dots, carbon dots, lipid nanoparticles and polymer-based nanocarriers, each offering unique benefits alongside specific challenges. Polymer-based nanocarriers, including hybrid and superparamagnetic nanoparticles, improve stability and functionality but are complex to manufacture. Polymeric nanoparticles with aggregation-induced emission (AIE) present promising theranostic potential for cancer detection and treatment. However, challenges such as translating the AIE concept to living systems, addressing toxicity concerns, overcoming deep-tissue imaging limitations, or ensuring biocompatibility remain to be resolved. Recently, cluster-triggered emission (CTE) polymers have emerged as innovative materials in nanotheranostics, offering enhanced fluorescence and biocompatibility. These polymers exhibit increased fluorescence intensity upon aggregation, making them highly sensitive for imaging and therapeutic applications. CTE nanoparticles, crafted from biodegradable polymers, represent a safer alternative to traditional nanotheranostics that rely on embedding conventional fluorophores or metal-based agents. This advancement significantly reduces potential toxicity while enhancing biocompatibility. The intrinsic fluorescence allows real-time monitoring of drug distribution and activity, optimizing therapeutic efficacy. Despite their potential, these systems face challenges such as maintaining stability under physiological conditions and addressing the need for comprehensive safety and efficacy studies to meet clinical and regulatory standards. Nevertheless, their unique properties position CTE nanoparticles as promising candidates for advancing theranostic strategies in personalized medicine, bridging diagnostic and therapeutic functionalities in innovative ways.

Journal of Nanotheranostics doi: 10.3390/jnt6010002

Authors: Galina M. Proshkina Elena I. Shramova Ekaterina V. Serova Egor A. Myachev Aziz B. Mirkasymov Sergey M. Deyev Alexander B. Kotlyar

Targeting HER2-positive cancer cells with precision therapies is a critical challenge in oncology. Here, we present a study on gold nanoparticles (AuNPs) conjugated with DARPin_9-29, a designed ankyrin repeat protein with high specificity and affinity for HER2 receptors. In this study, we investigate the therapeutic potential of AuNP-DARPin_9-29 conjugates, which was synthesized and characterized by us earlier, for photothermal therapy (PTT). By combining AuNP-DARPin treatment with visible light illumination, we show selective inhibition of HER2-positive cancer cell proliferation and tumor progression in a murine model. The results highlight the effectiveness of AuNP-DARPin in disrupting cancer cell viability and reducing tumor growth, providing a cost-effective and targeted approach for combating HER2-positive cancers.

Journal of Nanotheranostics doi: 10.3390/jnt6010001

Authors: Muneeb Ullah Uzma Azeem Awan Haider Ali Abdul Wahab Shahid Ullah Khan Muhammad Naeem Muhammad Ruslin Apon Zaenal Mustopa Nurhasni Hasan

Carbon dots (CDs) are a class of carbon-based nanomaterials undergoing rapid development with broad potential applications across diverse biomedical fields. These materials are highly attractive for diagnostics, therapeutics, and nanomedicine due to their remarkable optical and physicochemical properties, including photoluminescence, biocompatibility, and aqueous dispersibility. CDs can be synthesized using various techniques, ranging from top-down to bottom-up approaches. Among these, biogenic synthesis, utilizing natural sources and waste materials, presents an eco-friendly and sustainable alternative. CDs have exhibited considerable promise in diagnostics, especially with bioimaging and biosensing, providing both high sensitivity and precise identification. CDs are presently being investigated in the pharmaceutical sector for their potential applications in cancer and infection treatment, as well as in photodynamic and thermal therapies. The advancement of CD composites, through enhanced functionality and broader application, facilitates novel research in nanomedicine. This article highlights the advantages of CDs, focusing on their structural properties, classification, and versatility in synthesis methods. Furthermore, the safety and toxicity profiles of CDs are critically analyzed. In conclusion, the innocuity, adaptability, and multifunctionality of CDs position them as a cornerstone in the advancement of nanotechnology and biomedical applications. With their broad applicability and promising potential, CDs stand poised to drive significant innovation across diagnostics, therapeutics, and other domains, heralding a new era in nanomedicine and sustainable material development.

Journal of Nanotheranostics doi: 10.3390/jnt5040015

Authors: Nutan Rani Yousuf Khan Sapna Yadav Kalawati Saini Dipak Maity

Metal oxide nanoparticles (MONPs) have recently attracted much attention from researchers due to their use in cancer chemotherapy, targeted drug delivery, and diagnosis/MRI imaging. Various studies have demonstrated that different metal oxide NPs show cytotoxic effects by inducing apoptosis in cancerous cells and do not have any toxic impact on normal cells. The mechanism of cytotoxicity is shown through reactive oxygen species (ROS) generated by (MONPs) in the cancerous cell. In vitro and in vivo studies reveal that in some cases metal oxide NPs are used alone and somewhere these NPs are used in combination with other therapies such as photodynamic therapy and with anticancer nanomedicines as drug carriers or drug conjugates. The phenomenon of enhanced permeability and retention (EPR) effect has been the basis of targeted drug delivery to cancerous tumors. Finally, we also provide a simple and comparative analysis of the major apoptosis pathways proposed to increase beginner understanding of anti-cancer nanomaterials. Herein, we have reviewed the most important antitumor results obtained with different metal oxide nanoparticles such as ZnO, Fe2O3/Fe3O4, CuO/Cu2O, TiO2, CeO2, and HfO2, respectively. These NPs can be applied to treat cancer by either passive or active processes. A passive process uses the enhanced permeability and retention (EPR) effect. Superparamagnetic iron oxide nanoparticles (SPIONs), due to their unique magnetic and physiochemical properties have been used in magnetic fluid hyperthermia (MFH) and magnetic resonance imaging (MRI) in vitro as well as in vivo. Now, the research has reached the stage of clinical trials for the treatment of various types of cancer. ZnO NPs have been used very vastly in cytotoxic as well as in targeted drug delivery. These NPs are also used for loading anticancer drugs such as doxorubicin. Herein, in this review, we have examined current advances in utilizing MONPs and their analogs as cancer therapeutic, diagnostic, and drug-delivery agents.

Journal of Nanotheranostics doi: 10.3390/jnt5040014

Authors: Hossein Omidian Sumana Dey Chowdhury

Nanotheranostics, combining photothermal therapy (PTT) and photodynamic therapy (PDT), can transform precision cancer treatment by integrating diagnosis and therapy into a single platform. This review highlights recent advances in nanomaterials, drug delivery systems, and stimuli-responsive mechanisms for effective PTT and PDT. Multifunctional nanoparticles enable targeted delivery, multimodal imaging, and controlled drug release, overcoming the challenges posed by tumor microenvironments. Emerging approaches such as hybrid therapies and immune activation further enhance therapeutic efficacy. This paper discusses the limitations of nanotheranostics, including synthesis complexity and limited tissue penetration, and explores future directions toward biocompatible, scalable, and clinically translatable solutions.

Journal of Nanotheranostics doi: 10.3390/jnt5040013

Authors: Diana Corallo Cristina Nardelli Marcella Pantile Sara Menegazzo Alessandra Biffi Sanja Aveic

Neuroblastoma, the most common pediatric extracranial solid tumor, arises from the malignant transformation of neural crest progenitors in the peripheral nervous system. Its clinical and genetic heterogeneity poses significant challenges, especially in high-risk patients with metastatic disease. Two plastic neuroblastoma cell phenotypes, adrenergic (ADR) and mesenchymal (MES), have been identified. Notably, MES neuroblastoma cells exhibit increased migration and chemoresistance. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment further promote tumor aggressiveness by enhancing cancer cell proliferation, extracellular matrix remodeling, angiogenesis and metastasis. This study explored the role of non-activated fibroblasts in ADR and MES neuroblastoma cell proliferation, migration and invasion in vitro and in vivo. Results showed that MES and ADR neuroblastoma cells influenced fibroblast activation into CAFs differently, with MES cells promoting a more invasive environment leading to tumor spread. These findings enhance our understanding of how ADR and MES phenotypes contribute to the formation of a pro-metastatic niche by activating fibroblasts in CAFs. This insight could inform new therapeutic strategies targeting the tumor microenvironment to prevent neuroblastoma metastasis.

Journal of Nanotheranostics doi: 10.3390/jnt5040012

Authors: Marjorie de Carvalho Vieira Queiroz Luís Alexandre Muehlmann

Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have emerged as promising systems for delivering active ingredients. They are derived from physiological, biodegradable, and biocompatible lipids, offering benefits such as sustained release promotion and increased drug stability. These systems are apt for the efficient transport of therapeutic drugs to target tissues while also providing advantages such as facilitating large-scale industrial production, bioavailability, and protection against degradation. The preparation of these nanoparticles involves utilizing diverse types of lipids, surfactants, and solvents. Common lipid varieties encompass triglycerides, steroids, and fatty acids, selected based on the active ingredient for stabilization within the lipid matrix. Preparation methods can be categorized into high-energy and low-energy approaches. This study investigated the differences between the main methodologies used, comparing SLN and NLC systems, and scrutinizing their respective advantages, disadvantages, and applications.

Journal of Nanotheranostics doi: 10.3390/jnt5040011

Authors: Alexander Shao-Rong Pang Zi Qiang Glen Liau Jacob Yoong-Leong Oh Dinesh Kumar Srinivasan

Nanomaterials hold significant promise for the future of orthopaedic implants due to their ability to mimic the nanoscale components of the bone, such as collagen fibrils and hydroxyapatite. Nanomaterials can regulate cell behaviour while offering mechanical strength and biocompatibility, making them ideal for bone repair and tissue regeneration. This comprehensive review explores the key existing and potential applications of nanotechnology in orthopaedics, including bone tissue engineering, drug delivery systems, systems combatting implant-related infections, and the surface preparation of implants to enhance osseointegration. These innovations are poised to revolutionise orthopaedic care by improving implant durability, reducing infection risks, and promoting bone regeneration to deliver personalised treatment and create better patient outcomes.

Journal of Nanotheranostics doi: 10.3390/jnt5040010

Authors: Binapani Mahaling Namrata Baruah Aumreetam Dinabandhu

Infectious ocular diseases like keratitis, conjunctivitis, and endophthalmitis pose significant clinical challenges due to the complexities of delivering drugs to the eye. Recent advancements in drug delivery systems offer promising improvements for treating these conditions. Key strategies include targeted delivery through physicochemical modifications, magnetic nanoparticles, and ligand-receptor interactions. This review explores the safety and biocompatibility of ocular drug delivery systems through in vivo ocular toxicity studies, in vitro cytotoxicity assays, hemocompatibility studies, ocular tolerance tests, and genotoxicity assays. It also examines combination therapies and stimuli-responsive delivery systems for their potential to enhance therapeutic efficacy. Furthermore, we discuss tailored and optimized drug delivery approaches for infectious ocular diseases, outlining current challenges and future directions for developing effective ocular drug delivery systems.

Journal of Nanotheranostics doi: 10.3390/jnt5030009

Authors: Utibeabasi Ettah Sarah Jacques Dmitri Simberg

Ferumoxytol injection, also known as Feraheme®, is an approved IV injectable iron supplement and an experimental MRI contrast agent. Initially, it was approved as an IV bolus agent, but its use was later limited to a slow infusion drip due to high levels of infusion reactions. We collected various batches of ferumoxytol with expiration dates ranging from 2010 to 2025 and compared their size and zeta potential. Since nanoparticle surface properties can affect infusion reactions, we conducted a dot blot immunoassay to measure complement C3 opsonization with ferumoxytol preparations. We observed differences in nanoparticle size and zeta potential between batches and a 2.5-fold variation in complement activation. Interestingly, older batches from 2010 showed more uniform size distribution and lower complement activation than some of the newer batches. This finding may be valuable to the nanomedicine community and regulatory authorities.

Journal of Nanotheranostics doi: 10.3390/jnt5030008

Authors: Akanksha Nadkarni Dhwani Rana Nimeet Desai Derajram Benival Vishvesh Joshi Sagar Salave Dignesh Khunt

The escalating impact and remarkable progress of nanotechnology have shifted the paradigms of medicine and the healthcare system. Nanosystems have emerged, extensively holding the potential to advance disease diagnosis and treatment specificity. The extraordinary attributes imparted by nano-systems have helped in overcoming the limitations of conventional interventions to an extent and led to targeted therapy, to name one. The role of nanotechnology in diagnosis is another breakthrough in its appellation. This article aims to address the current characterization and sample preparation techniques for the analysis of nanosystems and provide insights into novel methodologies and in situ instrumentation that have eased sampling procedures.

Journal of Nanotheranostics doi: 10.3390/jnt5030007

Authors: Dmitri Simberg S. Moein Moghimi

PEGylation technology confers stability and modulates the biological performance of a broad range of preclinical and clinical nanopharmaceuticals. However, the emerging PEG immunogenicity in the general population is thought to impact the efficacy and safety of PEGylated medicines. Despite this, the clinical significance of PEG immunogenicity is still not clear and remains debatable. By considering the strategic importance of the PEGylation technology in nanopharmaceutical engineering, we raise a number of critical questions and briefly discuss gaps in the knowledge of PEG immunogenicity and its clinical significance.

Journal of Nanotheranostics doi: 10.3390/jnt5030006

Authors: Bohan Xu Shunjie Wu Yiyang Wang Yuhe Ji Shufeng Liang Chunyan Wang Xin Tian

Carbon nanotubes (CNTs), members of the nanomaterial family, are increasingly being used in consumer products and extensively studied for various biomedical applications. Due to their benign elemental composition, large surface area, and chemical and biological activities, CNTs demonstrate great potential in cancer therapy, including drug delivery, imaging analysis, photothermal therapy, photodynamic therapy, and radiotherapy. However, there is still a major knowledge gap when it comes to transitioning from research to clinical applications. One of the important issues is that the biological toxicity of CNTs, especially in terms of carcinogenesis, and the underlying mechanisms are not fully understood. Therefore, a thorough evaluation of toxicity and the underlying mechanisms of carcinogenesis is essential to enable the wide application of CNTs. In this review, we summarize the recent progress of CNTs as multifunctional therapeutics in cancer therapy. Furthermore, a detailed discussion is provided on the carcinogenesis and potential mechanisms of CNTs. Finally, the review ends with further challenges and prospects for CNTs with the expectation of facilitating their broader utilization.

Journal of Nanotheranostics doi: 10.3390/jnt5030005

Authors: Olavo O. Comparato Filho Marcela A. Cândido Aveline Ventura Flavia V. Morais Leandro Raniero

Deforestation is a common occurrence driven by agricultural expansion, urbanization, and infrastructure development. These activities often lead to increased human interaction with ecosystems, potentially exposing individuals to Paracoccidioides spores (P. brasiliensis and P. lutzii) found in the soil, resulting in Paracoccidioidomycosis (PCM). This fungal infection is endemic to specific regions in Latin America, such as Brazil, Colombia, Venezuela, and Argentina. Diagnosis typically involves a combination of clinical assessment, imaging techniques, and laboratory examinations. P. lutzii lacks the glycoprotein Gp43, a key antigenic protein utilized in serological tests for PCM diagnosis. In this study, a colorimetric test employing gold nanoparticles (AuNPs) and label-free methodology was employed for P. lutzii detection. The effectiveness of the label-free colorimetric test was assessed using a total of 100 samples. This detection was achieved through the amplification of the gp43 gene and the use of a specific probe (5′CAGGGGTGCG3′) in conjunction with AuNPs. The receiver operating characteristic curve was employed to assess the test, revealing that the method can accurately detect P. lutzii with a sensitivity of 100% and a specificity of 100%. The findings indicate a substantial impact on remote endemic regions attributable to the implementation of cost-effective diagnostic methodologies.

Journal of Nanotheranostics doi: 10.3390/jnt5020004

Authors: Masao Nakayama Hiroaki Akasaka Ryohei Sasaki Moshi Geso

Titanium dioxide nanoparticles (TiO2 NPs) have been investigated as one of the potential dose enhancement agents for radiation therapy. The role of TiO2 NPs as a photodynamic sensitiser has been well documented, but its sensitisation with X-rays is not highlighted. Unlike other metal NPs, such as gold NPs, the main challenge for TiO2 NPs as radiosensitisers is their low atomic number, resulting in a small cross-section for X-rays. This review summarises the results of current research in this area to explore the dose enhancement inflicted by TiO2 NPs, which could potentially be of great value in improving radiation therapy efficiency.

Journal of Nanotheranostics doi: 10.3390/jnt5020003

Authors: Panangattukara Prabhakaran Praveen Kumar Maggie Lee Taeho Kim

Nanotechnology advancements have resulted in many sensors and devices for biomedical applications. Among the various nanomaterials, gold nanoparticles (AuNPs), due to their size, shape, biocompatibility, and unique plasmonic property, are an excellent candidate for many biomedical applications. AuNPs, known for their easy surface modifications, robust nature, and photothermal activities, find application in drug delivery and cancer treatment studies. In this review, we are highlighting the recent trends in using AuNPs as nanomedicine for cancer immunotherapy. Cancer immunotherapy not only eliminates the primary tumors but also allows for the treatment of metastasis along with the recurrence of the tumor. AuNPs possess tissue-specific delivery functions that depend on the tunability in size and surface functionalization of AuNPs. AuNPs can be used to activate the tumor’s immune defense ability, or they can be used to enhance the anti-tumor immune response. Understanding the interaction of the tumor environment and nanobiomedicine is very important. In the present review, we give an idea of the mode of action of AuNPs and various combinations of therapies for cancer immunotherapy.

Journal of Nanotheranostics doi: 10.3390/jnt5010002

Authors: Fabio Pieretti Alessandro Moretto Emanuele Papini Regina Tavano

Graphene oxide (GO) nanoparticles, due to their favorable water solubility, compared to graphene (GA), are a hot research topic in biomedical and pharmaceutical research. However, GO clinical translation may be complicated by its high surface/volume ratio enhancing the interaction with human blood components. In fact, GO’s bi-dimensional nature and strong negative charge may lead to severe biological effects, such as thrombogenicity and immune cell activation. This study explores the impact of further GO surface chemical modulation on major adverse effects: blood plasma coagulation and hemolysis. To this aim, we refined GO nanoparticles by fine-tuned reduction chemistry, esterification and introduction of negative or positive charges. With this approach, we were able to mitigate plasma coagulation and hemolysis at variable degrees and to identify GO derivatives with improved biocompatibility. This opens the door to the progress of graphene-based nanotheranostic applications.

Journal of Nanotheranostics doi: 10.3390/jnt5010001

Authors: Daisy L. Wilson Jyoti Ahlawat Mahesh Narayan

The use of carbon nanomaterials including fullerenes, carbon nanotubes, carbon nano-onions, carbon dots and carbon quantum dots for environmental applications has increased substantially. These nanoparticles are now used in the development of sensors and switches, in agriculture as smart fertilizers and in the biomedical realm for cancer therapy intervention, as antioxidants, in gene delivery and as theranostics. Here, we review the role of fullerenes as neuroprotectants. Their sp2 hybridized architectures and ability to intervene in the soluble-to-toxic transformation of amyloidogenic trajectories is highlighted here, along with other physico–chemical properties that impact interventional efficacy. Also highlighted are drawbacks that need to be overcome and future prospects.

Journal of Nanotheranostics doi: 10.3390/jnt4040021

Authors: Elette Engels Michael Lerch Stéphanie Corde Moeava Tehei

Targeted brain cancer treatments are sorely needed to improve long-term prognosis, particularly for gliosarcoma and glioblastoma patients. Gold nanoparticles (GNPs) have unique properties including high atomic number, biocompatibility, and small size for cancer cell internalization. GNPs are consequently an ideal candidate for improved cancer targeting using image-guided radiotherapy. This work investigated 15 nm AuroVistTM GNPs for image-guided gliosarcoma radiotherapy and identified optimum GNP concentrations. The GNPs were found to be 15–20 nm using optical surface plasmon resonance absorption, with a (41.3 ± 0.3) nm hydrodynamic diameter. Confocal imaging showed that 50–500 µg/mL of the GNPs was well-internalized into the 9L cells within 24–48 h. γ-H2AX assays showed that 50–500 µg/mL of the GNPs radiosensitized the 9L cells irradiated with 125 and 150 kVp X-rays. However, only 500 µg/mL of the GNPs produced significant long-term dose enhancement with 150 kVp X-rays (with a sensitization enhancement ratio at 10% survival of 1.43, and 1.13 with 50 µg/mL) using clonogenic assay. CT imaging of the GNPs in the 9L tumors in Fischer rats further showed that GNP concentrations above 500 µg/mL were required to distinguish the tumor from the brain, and the GNPs were detected 48 h after injection. These promising results indicate that the GNPs can be used for selective gliosarcoma treatment with image-guided X-ray radiotherapy at concentrations above 500 µg/mL.

Journal of Nanotheranostics doi: 10.3390/jnt4040020

Authors: Kelly Schwinghamer Teruna J. Siahaan

Antibodies (mAbs) are attractive molecules for their application as a diagnostic and therapeutic agent for diseases of the central nervous system (CNS). mAbs can be generated to have high affinity and specificity to target molecules in the CNS. Unfortunately, only a very small number of mAbs have been specifically developed and approved for neurological indications. This is primarily attributed to their low exposure within the CNS, hindering their ability to reach and effectively engage their potential targets in the brain. This review discusses aspects of various barriers such as the blood–brain barrier (BBB) and blood–cerebrospinal fluid (CSF) barrier (BCSFB) that regulate the entry and clearance of mAbs into and from the brain. The roles of the glymphatic system on brain exposure and clearance are being described. We also discuss the proposed mechanisms of the uptake of mAbs into the brain and for clearance. Finally, several methods of enhancing the exposure of mAbs in the CNS were discussed, including receptor-mediated transcytosis, osmotic BBB opening, focused ultrasound (FUS), BBB-modulating peptides, and enhancement of mAb brain retention.

Journal of Nanotheranostics doi: 10.3390/jnt4030019

Authors: Unnati Patel Emily C. Hunt

In recent years, antimicrobial resistance in many human pathogens has become a serious health concern. Since infections with resistant pathogens cannot be treated with traditional antimicrobial drugs, new strategies are necessary to fight bacterial infections. Hybrid nano-systems may provide a solution to this problem, by combining multiple mechanisms for killing bacteria to synergistically increase the effectiveness of the antimicrobial treatment. In this review, we highlight recent advances in the development of hybrid nano-systems for the treatment of bacterial infections. We discuss the use of hybrid nano-systems for combinational therapy, focusing on various triggering mechanisms for drug release and the development of biomimetic nanomaterials. We also examine inherently antimicrobial nano-systems and their uses in preventing infections due to wounds and medical implants. This review summarizes recent advances and provides insight into the future development of antimicrobial treatments using hybrid nanomaterials.

Journal of Nanotheranostics doi: 10.3390/jnt4030018

Authors: Manish Ramchandani Priyanka Kumari Amit K. Goyal

Cardiovascular disease (particularly atherosclerosis) is a leading cause of death around the world, and there still exists a need for improved diagnostic techniques and treatments to improve patient outcomes as well as minimize the disease’s global burden. Aptamers are short, single-stranded DNA or RNA molecules that are accompanied by unique characteristics such as specificity, high binding affinity, ease of cellular internalization, and rapid tissue accumulation capabilities, offering great potential as theranostic agents in cardiovascular diseases with significantly improved sensitivity and accuracy. These theranostic agents provide a combination of therapy and diagnostics in which aptamers may diagnose and treat disease simultaneously. Therefore, this review article summarizes the role of aptamer-based probes for imaging and theranostics in cardiovascular disease. It also provides insight into current research and future treatment techniques that are very relevant for future clinical practice with the aim of improving the quality of life of cardiovascular disease patients.

Journal of Nanotheranostics doi: 10.3390/jnt4030017

Authors: Akash Kumar Nabojit Das Raja Gopal Rayavarapu

A significant paradigm shift has been observed in the past decade in the area of theranostics owing to the development of various isotropic and anisotropic metal nanostructures, simultaneous with improved imaging modalities. Platinum-based nanostructures are advancing in a plethora of clinical applications as theranostics tools owing to their unique behavior concerning their size, shape, and surface chemistry at the nanoscale regime. Platinum nanostructures are optically active and provide significant potential to the field of theranostics by simplifying diagnosis and therapeutics, thus providing key solutions through nano-enabled technologies. The review emphasizes the potential of platinum nanostructures that have immense potential in vitro and in vivo scenarios as nanocarriers. Still, their potential in terms of photothermal active agents has not been well explored or reported. Nanotheranostics has emerged as a platform where various noble metal nanoparticles are effectively efficient as photothermal agents in bringing precision to therapy and diagnostics. Platinum, as an antioxidant and a stable nanocarrier, will enable them to act as photosensitizers when conjugated to affinity molecules and plays a key role in efficient treatment and diagnosis. The review envisions bringing together the possibilities of the safe-by-design synthesis of platinum nanostructures and their potential role in both in vitro and in vivo applications. A roadmap describing the challenges, pitfalls, and possibilities of influencing platinum nanostructures to overcome the existing biological/targeting barriers is elaborated. This review provides a literature survey on platinum nanostructures in theranostics, providing novel strategies in bio-imaging, diagnostics, and nanomedicine.

Journal of Nanotheranostics doi: 10.3390/jnt4030016

Authors: Paul A. Akpa Ikechukwu E. Peter Akachukwu M. Onwuka Bonaventure C. Obi Maureen O. Akunne Chukwuemeka S. Nworu Paul M. Ejikeme Theophine C. Akunne Anthony A. Attama Peter A. Akah

Globally, cancer is one of the deadliest diseases, needing a meticulous diagnosis and targeted treatment plan to achieve an initial prognosis, followed by precision and optimization in treatment. Nonselective targeting, difficulty in accurately monitoring treatment end-results, serious drug side-effects, and severity of disease resulting in metastasis are the key flaws of traditional techniques. Nanotechnology and nanoparticles possess special features to completely transform the field of diagnosis and treatment of cancer. A holistic strategy that employs a dual function of diagnosis and therapy while utilizing a nanocarrier is referred to as a nanotheranostic. The nanotheranostic framework was created to surmount a variety of biological and physiological obstacles, effectively delivering the cargo to the intended target location, while simultaneously facilitating therapeutic intervention, surveillance, and validation to demonstrate improved treatment effectiveness. As a result, a nanotheranostic platform can be useful for targeted drug delivery, release, and distribution assessment, in addition to patient classification and survival. Nanotheranostic techniques also lead to reduced drug side-effects compared with conventional therapies. In this review, we outline current studies on nanotheranostics and their advantages over conventional treatment strategies, the applications and challenges/limitations of nanotheranostics, and the mechanisms of targeting in breast and prostate cancers.

Journal of Nanotheranostics doi: 10.3390/jnt4030015

Authors: William H. Pentz Vincenzo J. Pizzuti Matthew E. Halbert Tritan J. Plute Paul R. Lockman Samuel A. Sprowls

Glioblastoma is the most common primary, malignant brain tumor that remains uniformly lethal in nearly all cases as a result of extreme cellular heterogeneity, treatment resistance, and recurrence. A major hurdle in therapeutic delivery to brain tumors is the blood–brain barrier (BBB), which is the tightly regulated vascular barrier between the brain parenchyma and systemic circulation that prevents distribution of otherwise beneficial chemotherapeutics to central nervous system tumors. To overcome the obstacle of drug delivery beyond the BBB, nanoparticle formulations have come to the forefront, having demonstrated success in preclinical observations, but have not translated well into the clinical setting. In summary, this review article discusses brain tumors and challenges for drug delivery caused by the BBB, explores the benefits of nanoparticle formulations for brain tumor delivery, describes the characteristics these formulations possess that make them attractive therapeutic strategies, and provides preclinical examples that implement nanoparticles within glioma treatment regimens. Additionally, we explore the pitfalls associated with clinical translation and conclude with remarks geared toward overcoming these issues.

Journal of Nanotheranostics doi: 10.3390/jnt4030014

Authors: Divya Tripathi Kasturee Hajra Dipak Maity

The introduction of cancer therapeutics and nanotechnology has resulted in a paradigm shift from conventional therapy to precision medicine. Nanotechnology, an interdisciplinary field with a focus on biomedical applications, holds immense promise in bringing about novel approaches for cancer detection, diagnosis, and therapy. The past decade has witnessed significant research and material applications related to nanoparticles (NPs). NPs differ from small-molecule drugs as they possess unique physicochemical characteristics, such as a large surface-to-volume ratio, enabling them to penetrate live cells efficiently. Traditional cancer therapies, such as chemotherapy, radiation therapy, targeted therapy, and immunotherapy, have limitations, such as cytotoxicity, lack of specificity, and multiple drug resistance, which pose significant challenges for effective cancer treatment. However, nanomaterials have unique properties that enable new therapeutic modalities beyond conventional drug delivery in the fight against cancer. Moreover, nanoparticles (1–100 nm) have numerous benefits, such as biocompatibility, reduced toxicity, excellent stability, enhanced permeability and retention effect, and precise targeting, making them ideal for cancer treatment. The purpose of this article is to provide consolidated information on various bio-inspired nanoparticles that aid in cancer theranostics.

Journal of Nanotheranostics doi: 10.3390/jnt4030013

Authors: Kaushita Banerjee Harishkumar Madhyastha

Nanomaterial-based tissue engineering strategies are precisely designed and tweaked to contest specific patient needs and their end applications. Though theragnostic is a radical term very eminent in cancer prognosis, of late, theragnostic approaches have been explored in the fields of tissue remodulation and reparation. The engineering of theragnostic nanomaterials has opened up avenues for disease diagnosis, imaging, and therapeutic treatments. The instantaneous monitoring of therapeutic strategy is expected to co-deliver imaging and pharmaceutical agents at the same time, and nanoscale carrier moieties are convenient and efficient platforms in theragnostic applications, especially in soft and hard tissue regeneration. Furthermore, imaging modalities have extensively contributed to the signal-to-noise ratio. Simultaneously, there is an accumulation of high concentrations of therapeutic mediators at the defect site. Given the confines of contemporary bone diagnostic systems, the clinical rationale demands nano/biomaterials that can localize to bone-diseased sites to enhance the precision and prognostic value for osteoporosis, non-healing fractures, and/or infections, etc. Furthermore, bone theragnostics may have an even greater clinical impact and multimodal imaging procedures can overcome the restrictions of individual modalities. The present review introduces representative theragnostic polymeric nanomaterials and their advantages and disadvantages in practical use as well as their unique properties.

Journal of Nanotheranostics doi: 10.3390/jnt4030012

Authors: Shaikh Sheeran Naser Basab Ghosh Faizan Zarreen Simnani Dibyangshee Singh Anmol Choudhury Aditya Nandi Adrija Sinha Ealisha Jha Pritam Kumar Panda Mrutyunjay Suar Suresh K. Verma

Zinc oxide nanomaterials have been the cynosure of this decade because of their immense potential in different biomedical applications. It includes their usage in the prognosis and treatment of different infectious and cellular diseases, owing to their peculiar physiochemical properties such as variable shape, size, and surface charge etc. Increasing demand and usage of the ZnO nanomaterials raise concerns about their cellular and molecular toxicity and their biocompatibility with human cells. This review comprehensively details their physiochemical properties for usage in biomedical applications. Furthermore, the toxicological concerns of ZnO nanomaterials with different types of cellular systems have been reviewed. Moreover, the biomedical and biocompatible efficacy of ZnO nanomaterials for cancer specific pathways has been discussed. This review offers insights into the current scenario of ZnO nanomaterials usage and signifies their potential future extension usage on different types of biomedical and environmental applications.

Journal of Nanotheranostics doi: 10.3390/jnt4030011

Authors: Mohamed Talaat Jensen Xi Kaiyuan Tan Xiuhua April Si Jinxiang Xi

Aerosols exhaled from the lungs have distinctive patterns that can be linked to the abnormalities of the lungs. Yet, due to their intricate nature, it is highly challenging to analyze and distinguish these aerosol patterns. Small airway diseases pose an even greater challenge, as the disturbance signals tend to be weak. The objective of this study was to evaluate the performance of four convolutional neural network (CNN) models (AlexNet, ResNet-50, MobileNet, and EfficientNet) in detecting and staging airway abnormalities in small airways using exhaled aerosol images. Specifically, the model’s capacity to classify images inside and outside the original design space was assessed. In doing so, multi-level testing on images with decreasing similarities was conducted for each model. A total of 2745 images were generated using physiology-based simulations from normal and obstructed lungs of varying stages. Multiple-round training on datasets with increasing images (and new features) was also conducted to evaluate the benefits of continuous learning. Results show reasonably high classification accuracy on inbox images for models but significantly lower accuracy on outbox images (i.e., outside design space). ResNet-50 was the most robust among the four models for both diagnostic (2-class: normal vs. disease) and staging (3-class) purposes, as well as on both inbox and outbox test datasets. Variation in flow rate was observed to play a more important role in classification decisions than particle size and throat variation. Continuous learning/training with appropriate images could substantially enhance classification accuracy, even with a small number (~100) of new images. This study shows that CNN transfer-learning models could detect small airway remodeling (<1 mm) amidst a variety of variants and that ResNet-50 can be a promising model for the future development of obstructive lung diagnostic systems.

Journal of Nanotheranostics doi: 10.3390/jnt4030010

Authors: Sourour Idoudi Roua Ismail Ousama Rachid Abdelbary Elhissi Alaaldin M. Alkilany

Gold nanoparticles (AuNP) have received a growing attention due to their fascinating physiochemical properties and promising range of biomedical applications including sensing, diagnosis and cancer photothermal ablation. AuNP enjoy brilliant optical properties and ability to convert light into local heat and function as a “nanoheaters” to fight cancer. However, AuNP are poor drug delivery systems as they do not have reservoirs or matrices to achieve an acceptable drug loading efficiency. On the other end, liposome-based nanocarriers do not exhibit such optical properties but are excellent platform for drug loading and they have been proven clinically with a true presence in the market since the FDA approved Doxil® in 1995. Combining the brilliant optical and photothermal properties of AuNP with the excellent drug loading capability of liposome should yield nanocomposites that enjoy the features of both modalities and enable the development of novel and smart drug delivery systems. Therefore, this review discusses the up-to date research on the AuNP-liposome nanocomposites and the current available approaches and protocols for their preparation and characterization. Finally, the biomedical applications of AuNP-liposome nanocomposites and proposed future directions in this field are discussed.

Journal of Nanotheranostics doi: 10.3390/jnt4020009

Authors: Johnson Hoang Pooria Tajalli Mina Omidiyan Maria D. Marquez Orawan Khantamat Wirote Tuntiwechapikul Chien-Hung Li Arati Kohlhatkar Hung-Vu Tran Preethi H. Gunaratne T. Randall Lee

MicroRNA (miRNA) has emerged as a promising alternative therapeutic treatment for cancer, but its delivery has been hindered by low cellular uptake and degradation during circulation. In this review, we discuss the various methods of delivering miRNA, including viral and non-viral delivery systems such as liposomes and nanoparticles. We also examine the use of nanoparticles for miRNA-based diagnostics. We focus specifically on non-viral delivery systems utilizing coinage metals in the form of nanoparticles and the use of self-assembled monolayers (SAMs) as a method of surface modification. We review the use of SAMs for the conjugation and delivery of small noncoding ribonucleic acid (ncRNA), particularly SAMs derived from positively charged adsorbates to generate charged surfaces that can interact electrostatically with negatively charged miRNA. We also discuss the effects of the cellular uptake of gold and other plasmonic nanoparticles, as well as the challenges associated with the degradation of oligonucleotides. Our review highlights the potential of SAM-based systems as versatile and robust tools for delivering miRNA and other RNAs in vitro and in vivo and the need for further research to address the challenges associated with miRNA delivery and diagnostics.

Journal of Nanotheranostics doi: 10.3390/jnt4020008

Authors: Dhiraj Kumar Isha Mutreja Ajeet Kaushik

The limitations of current treatment strategies for cancer management have prompted a significant shift in the research and development of new effective strategies exhibiting higher efficacy and acceptable side effects. In this direction, nanotheranostics has gained significant interest in recent years, combining the diagnostic and therapeutic capabilities of nanostructures for efficient disease diagnosis, treatment, and management. Such nano-assisted platforms permit the site-specific release of bioactive cargo in a controlled fashion while permitting non-invasive real-time in situ monitoring. A plethora of materials has been developed as pharmacologically relevant nanoformulations for theranostic applications ranging from metallic to lipid and polymer-based composite systems, with each offering potential opportunities and its own limitations. To improve advancements with better clarity, the main focus of this review is to highlight the recent developments focusing on using different noble metal nanoparticles (noble MNPs) as cancer nanotheranostic agents, highlighting their properties, advantages, and potential modifications for their successful utilization in personalized medicine. The advantage of using noble metals (not all, but those with an atomic number ≥76) over metal NPs is their tendency to provide additional properties, such as X-ray attenuation and near-infrared activity. The combination of these properties translates to noble MNPs for therapeutic and diagnostic applications, independent of the need for additional active molecules. Through this review, we highlighted the potential application of all noble MNPs and the limited use of osmium, iridium, palladium, rhodium, and ruthenium metal NSs, even though they express similar physicochemical characteristics. The literature search was limited by PubMed, full-text availability, and studies including both in vitro and in vivo models.

Journal of Nanotheranostics doi: 10.3390/jnt4020007

Authors: Maria Anthi Kouri Konstantina Polychronidou Grigorios Loukas Aikaterini Megapanou Ioanna-Aglaia Vagena Angelica M. Gerardos Ellas Spyratou Eftstathios P. Eftsathopoulos

The multifactorial nature of cancer still classifies the disease as one of the leading causes of death worldwide. Modern medical sciences are following an interdisciplinary approach that has been fueled by the nanoscale revolution of the past years. The exploitation of high-Z materials, in combination with ionizing or non-ionizing radiation, promises to overcome restrictions in medical imaging and to augment the efficacy of current therapeutic modalities. Gold nanoparticles (AuNPs) have proven their value among the scientific community in various therapeutic and diagnostic techniques. However, the high level of multiparametric demands of AuNP experiments in combination with their biocompatibility and cytotoxicity levels remain crucial issues. Gadolinium NPs (GdNPs), have presented high biocompatibility, low cytotoxicity, and excellent hemocompatibility, and have been utilized in MRI-guided radiotherapy, photodynamic and photothermal therapy, etc. Τhe utilization of gadolinium bound to AuNPs may be a promising alternative that would reduce phenomena, such as toxicity, aggregation, etc., and could create a multimodal in vivo contrast and therapeutic agent. This review highlights multi-functionalization strategies against cancer where gold and gadolinium NPs are implicated. Their experimental applications and limitations of the past 5 years will be analyzed in the hope of enlightening the benefits and drawbacks of their proper combination.

Journal of Nanotheranostics doi: 10.3390/jnt4010006

Authors: Amit K. Goyal Manish Ramchandani Trambak Basak

As of today, chronic inflammatory diseases are a progressive cause of death worldwide, accounting for more than 50% of all fatalities. These inflammatory conditions are a major concern, ranging from heart disease to cancer, diabetes, to even neurodegenerative conditions. Conventional diagnosis and treatment for these problems are often challenging and limited due to complex pathophysiology. To improve upon current treatment and diagnostic strategies, theranostic nanomaterials have been developed. Theranostics is an amalgamation of diagnostic biomarkers and therapeutic medicines that have a shared target in damaged cells or tissues. Different theranostic nanoparticles generate enhanced imaging results for facilities such as MRI, PET scan, and CT scans depending on the site of inflammation in different organs. Furthermore, they can be treated with radiopharmaceuticals and/or medicine in nanoparticles. Following a brief discussion of conventional inflammatory diagnosis and therapeutic strategies, this review will cover the recent progress made in theranostic nanomaterials and nanomedicine tactics for managing inflammatory disorders, covering the preclinical and clinical stages of these advances from the past five years. Furthermore, present challenges with theranostic nanoparticles for inflammatory detection and treatment are discussed, as well as future research possibilities.

Journal of Nanotheranostics doi: 10.3390/jnt4010005

Authors: Ellas Spyratou Kyriakos Kokkinogoulis Georgios Tsigaridas Georgios Kareliotis Kalliopi Platoni Mersini Makropoulou Efstathios P. Efstathopoulos

In oncology, tremendous research has been conducted on the use of alternative minimally invasive techniques for cancer treatment and diagnosis. The use of biophotonic techniques as a standalone treatment or together with conventional imaging techniques has gained interest among researchers in recent years, while biophotonic therapies such as photothermal and photodynamic therapies tend to bring the use of non-ionizing radiation in therapy back into the spotlight due to the progressive development of optical instrumentation, enhancement agents, molecular probes, light sources and nanocarriers. Thus, the coupling of non-ionizing with ionizing radiation (IR) and the combination of nanomedicine with nuclear medicine procedures are considered to be revolutionary strategies to optimize the therapeutic efficacy of biophotonic modalities and to develop theranostic applications for the better diagnosis and treatment of cancer. Recently, the low-intensity Cerenkov light emitted by tissues as a byproduct of the IR–biostructure interaction has been suggested as an effective internal light source that can trigger phototherapy and guide radiotherapy dosimetry using Cerenkov imaging. This review also provides an overview of in vitro and in vivo studies regarding the use of Cerenkov radiation produced by X-rays or radionucleotides and combined with nanoparticles as a hybrid method to induce enhanced photothermal and photodynamic therapies.

Journal of Nanotheranostics doi: 10.3390/jnt4010004

Authors: Vaishali Pawar Priyanka Maske Amreen Khan Arnab Ghosh Roshan Keshari Mahek Bhatt Rohit Srivastava

Currently, intelligent, responsive biomaterials have been widely explored, considering the fact that responsive biomaterials provide controlled and predictable results in various biomedical systems. Responsive nanostructures undergo reversible or irreversible changes in the presence of a stimulus, and that stimuli can be temperature, a magnetic field, ultrasound, pH, humidity, pressure, light, electric field, etc. Different types of stimuli being used in drug delivery shall be explained here. Recent research progress in the design, development and applications of biomaterials comprising responsive nanostructures is also described here. More emphasis will be given on the various nanostructures explored for the smart stimuli responsive drug delivery at the target site such as wound healing, cancer therapy, inflammation, and pain management in order to achieve the improved efficacy and sustainability with the lowest side effects. However, it is still a big challenge to develop well-defined responsive nanostructures with ordered output; thus, challenges faced during the design and development of these nanostructures shall also be included in this article. Clinical perspectives and applicability of the responsive nanostructures in the targeted drug delivery shall be discussed here.

Journal of Nanotheranostics doi: 10.3390/jnt4010003

Authors: Sarah Vogel Alice O’Keefe Léa Seban Michael Valceski Elette Engels Abass Khochaiche Carolyn Hollis Michael Lerch Stéphanie Corde Christophe Massard Komla Oscar Awitor Moeava Tehei

Gold nanoparticles are a promising candidate for developing new strategies of therapy against cancer. Due to their high atomic number and relative biocompatibility, they are commonly investigated as radiosensitizers to locally increase the dose of radiotherapy. In order to optimize this radiosensitizing effect, it is necessary to control the positioning of the nanoparticles in the cells. The purpose of this study is to investigate, by means of fluorescent gold nanoparticles in suspension, the dose enhancement on highly radio-resistant cancer cells. These nanoparticles were successfully produced using modern click-chemistry methods, first by attaching a chelating agent Diethylenetriamine pentaacetate benzylamine to L-cysteine, bonding the resulting ligand to a gold core, grafting propargylamine and then utilizing copper-catalyzed azide-alkyne cycloaddition (CuAAC) to fuse AlexaFluor 647 to the ligands. The results of this study prove the success of the reactions to produce a minimally cytotoxic and highly stable nanoparticle suspension that increases the radiosensitivity of gliosarcoma 9L tumor cells, with a 35% increase in cell death using 5 Gy kilovoltage radiation. Their fluorescent functionalization allowed for their simple localization within living cells and detection in vivo post-mortem.

Journal of Nanotheranostics doi: 10.3390/jnt4010002

Authors: Chiara Martinelli Emanuela Jacchetti

The application of biocompatible nanomaterials to simultaneously detect and provide treatment of a disease is referred to as nanotheranostics [...]

Journal of Nanotheranostics doi: 10.3390/jnt4010001

Authors: Akash Kumar Nabojit Das Raja Gopal Rayavarapu

The existing diagnosis and treatment modalities have major limitations related to their precision and capability to understand several stages of disease development. A superior therapeutic system consists of a multifunctional approach in early diagnosis of the disease with a simultaneous progressive cure, using a precise medical approach towards complex treatment. These challenges can be addressed via nanotheranostics and explore suitable approaches to improve health care. Nanotechnology in combination with theranostics as an unconventional platform paved the way for developing novel strategies and modalities leading to diagnosis and therapy for complex disease conditions, ranging from acute to chronic levels. Among the metal nanoparticles, gold nanoparticles are being widely used for theranostics due to their inherent non-toxic nature and plasmonic properties. The unique optical and chemical properties of plasmonic metal nanoparticles along with theranostics have led to a promising era of plausible early detection of disease conditions, and they enable real-time monitoring with enhanced non-invasive or minimally invasive imaging of several ailments. This review aims to highlight the improvement and advancement brought to nanotheranostics by gold nanoparticles in the past decade. The clinical use of the metal nanoparticles in nanotheranostics is explained, along with the future perspectives on addressing the key applications related to diagnostics and therapeutics, respectively. The scope of gold nanoparticles and their realistic potential to design a sophisticated theranostic system is discussed in detail, along with their implications in clinical advancements which are the needs of the hour. The review concluded with the challenges, opportunities, and implications on translational potential of using gold nanoparticles in nanotheranostics.

Journal of Nanotheranostics doi: 10.3390/jnt3040014

Authors: Ibrahim A. Shehu Muhammad K. Musa Aparna Datta Amita Verma

There is an urgent need to address the global mortality of the COVID-19 pandemic, as it reached 6.3 million as of July 2022. As such, the experts recommended the mass diagnosis of SARS-CoV-2 infection at an early stage using nanotechnology-based sensitive diagnostic approaches. The development of nanobiosensors for Point-of-Care (POC) sampling of COVID-19 could ensure mass detection without the need for sophisticated laboratories or expert personnel. The use of Artificial Intelligence (AI) techniques for POC detection was also proposed. In addition, the utilization of various antiviral nanomaterials such as Silver Nanoparticles (AgNPs) for the development of masks for personal protection mitigates viral transmission. Nowadays, nano-assisted vaccines have been approved for emergency use, but their safety and effectiveness in the mutant strain of the SARS-CoV-2 virus remain challenging. Methodology: Updated literature was sourced from various research indexing databases such as PubMed, SCOPUS, Science Direct, Research Gate and Google Scholars. Result: We presented the concept of novel nanotechnology researched discovery, including nano-devices, electrochemical biosensing, nano-assisted vaccine, and nanomedicines, for use in recent times, which could be a formidable step for future management of COVID-19.

Journal of Nanotheranostics doi: 10.3390/jnt3040013

Authors: Sanduru Thamarai Krishnan David Rudd Rana Rahmani E. Eduardo Antunez Rajpreet Singh Minhas Chandra Kirana Guy J. Maddern Kevin Fenix Ehud Hauben Nicolas H. Voelcker

Despite improvements in treatment options for advanced colorectal cancer (CRC), survival outcomes are still best for patients with non-metastasised disease. Diagnostic tools to identify blood-based biomarkers and assist in CRC subtype classification could afford a means to track CRC progression and treatment response. Cancer cell-derived small extracellular vesicles (EVs) circulating in blood carry an elevated cargo of lipids and proteins that could be used as a signature of tumour suppressor/promoting events or stages leading up to and including metastasis. Here, we used pre-characterised biobanked plasma samples from surgical units, typically with a low volume (~100 µL), to generate and discover signatures of CRC-derived EVs. We employed nanostructured porous silicon (pSi) surface assisted-laser desorption/ionisation (SALDI) coupled with high-resolution mass spectrometry (HR-MS), to allow sensitive detection of low abundant analytes in plasma EVs. When applied to CRC samples, SALDI-HR-MS enabled the detection of the peptide mass fingerprint of cancer suppressor proteins, including serine/threonine phosphatases and activating-transcription factor 3. SALDI-HR-MS also allowed the detection of a spectrum of glycerophospholipids and sphingolipid signatures in metastatic CRC. We observed that lithium chloride enhanced detection sensitivity to elucidate the structure of low abundant lipids in plasma EVs. pSi SALDI can be used as an effective system for label-free and high throughput analysis of low-volume patient samples, allowing rapid and sensitive analysis for CRC classification.

Journal of Nanotheranostics doi: 10.3390/jnt3040012

Authors: Omer Gal Oshra Betzer Liat Rousso-Noori Tamar Sadan Menachem Motiei Maxim Nikitin Dinorah Friedmann-Morvinski Rachela Popovtzer Aron Popovtzer

Background: Glioblastoma is the most lethal primary brain malignancy in adults. Standard of care treatment, consisting of temozolomide (TMZ) and adjuvant radiotherapy (RT), mostly does not prevent local recurrence. The inability of drugs to enter the brain, in particular antibody-based drugs and radiosensitizers, is a crucial limitation to effective glioblastoma therapy. Methods: Here, we developed a combined strategy using radiosensitizer gold nanoparticles coated with insulin to cross the blood–brain barrier and shuttle tumor-targeting antibodies (cetuximab) into the brain. Results: Following intravenous injection to an orthotopic glioblastoma mouse model, the nanoparticles specifically accumulated within the tumor. Combining targeted nanoparticle injection with TMZ and RT standard of care significantly inhibited tumor growth and extended survival, as compared to standard of care alone. Histological analysis of tumors showed that the combined treatment eradicated tumor cells, and decreased tumor vascularization, proliferation, and repair. Conclusions: Our findings demonstrate radiosensitizer nanoparticles that effectively deliver antibodies into the brain, target the tumor, and effectively improve standard of care treatment outcome in glioblastoma.

Journal of Nanotheranostics doi: 10.3390/jnt3040011

Authors: Unnati Patel Kavini Rathnayake Emily C. Hunt Nirupama Singh

Facing the deadly pandemic caused by the SARS-CoV-2 virus all over the globe, it is crucial to devote efforts to fighting and preventing this infectious virus. Nanomaterials have gained much attention after the approval of lipid nanoparticle-based COVID-19 vaccines by the United States Food and Drug Administration (USFDA). In light of increasing demands for utilizing nanomaterials in the management of COVID-19, this comprehensive review focuses on the role of nanomaterials in the prevention, diagnostics, therapeutics, and vaccine development of COVID-19. First, we highlight the variety of nanomaterials usage in the prevention of COVID-19. We discuss the advantages of nanomaterials as well as their uses in the production of diagnostic tools and treatment methods. Finally, we review the role of nanomaterials in COVID-19 vaccine development. This review offers direction for creating products based on nanomaterials to combat COVID-19.

Journal of Nanotheranostics doi: 10.3390/jnt3030010

Authors: Katerina Spyridopoulou Georgios Aindelis Charalampos Sarafidis Orestis Kalogirou Katerina Chlichlia

The application of magnetomechanical stress in cells using internalized magnetic nanoparticles (MNPs) actuated by low-frequency magnetic fields has been attracting considerable interest in the field of cancer research. Recent developments prove that magnetomechanical stress can inhibit cancer cells’ growth. However, the MNPs’ type and the magnetic field’s characteristics are crucial parameters. Their variability allows multiple combinations, which induce specific biological effects. We previously reported the antiproliferative effects induced in HT29 colon cancer cells by static-magnetic-field (200 mT)-actuated spherical MNPs (100 nm). Herein, we show that similar growth inhibitory effects are induced in other colon cancer cell lines. The effect of magnetomechanical stress was also examined in the growth rate of tumor spheroids. Moreover, we examined the biological mechanisms involved in the observed cell growth inhibition. Under the experimental conditions employed, no cell death was detected by PI (propidium iodide) staining analysis. Flow cytometry and Western blotting revealed that G2/M cell cycle arrest might mediate the antiproliferative effects. Furthermore, MNPs were found to locate in the lysosomes, and a decreased number of lysosomes was detected in cells that had undergone magnetomechanical stress, implying that the mechanical activation of the internalized MNPs could induce lysosome membrane disruption. Of note, the lysosomal acidic conditions were proven to affect the MNPs’ magnetic properties, evidenced by vibrating sample magnetometry (VSM) analysis. Further research on the combination of the described magnetomechanical stress with lysosome-targeting chemotherapeutic drugs could lay the groundwork for the development of novel anticancer combination treatment schemes.

Journal of Nanotheranostics doi: 10.3390/jnt3030009

Authors: S. Moein Moghimi Simó Schwartz

Circulating tumour cells (CTCs) with stem cell-like properties and epithelial-mesenchymal transition phenotype are precursor cells responsible for dissemination and metastatic spread of cancer [...]

Journal of Nanotheranostics doi: 10.3390/jnt3020008

Authors: Yao-Chen Chuang Hsin-Lun Lee Jeng-Fong Chiou Leu-Wei Lo

Gold nanoparticle (AuNPs)-mediated photothermal therapy (PTT) has attracted increasing attention both in laboratory research and clinical applications. Due to its easily-tuned properties of irradiation light and inside-out hyperthermia ability, it has demonstrated clear advantages in cancer therapy over conventional thermal ablation. Despite this great advancement, the therapeutic efficacy of AuNPs mediated PTT in tumor treatment remains compromised by several obstacles, including low photothermal conversion efficiency, tissue penetration limitation of excitation light, and inherent non-specificity. In view of the rapid development of AuNPs mediated PTT, we present an in-depth review of major breakthroughs in the advanced development of gold nanomaterials for PTT, with emphasis on those from 2010 to date. In particular, the current state of knowledge for AuNPs based photothermal agents within a paradigm of key structure-optical property relationships is presented in order to provide guidance for the design of novel AuNP based photothermal agents to meet necessary functional requirements in specific applications. Furthermore, potential challenges and future development of AuNP mediated PTT are also elucidated for clinical translation. It is expected that AuNP mediated PTT will soon constitute a markedly promising avenue in the treatment of cancer.

Journal of Nanotheranostics doi: 10.3390/jnt3020007

Authors: Suhash Reddy Chavva Namratha Bhat Angela Michelle T. San Juan Siddhant Jaitpal Samuel Mabbott

Gold nanoparticles absorb light energy and convert it to thermal energy that transfers to the surrounding environment, making them potentially useful for the hyperthermic treatments well known as photothermal therapy (PTT). Further, it is well documented that noble metal nanoparticles are capable of significantly enhancing the Raman scattering of molecules attached to their surfaces, a technique which is termed surface-enhanced Raman scattering (SERS). SERS combined with PTT has the ability to locate nanoparticles at depth and trigger heat production, providing an effective methodology to both seek and destroy diseased tissues. While PTT and SERS are often used in tandem and there are several ways of individually measuring SERS and thermal output, there is currently no method available that pre-screens both properties prior to in vitro or in vivo application. In this work, we have designed a 3D printed platform capable of coupling a commercially available Raman probe to a sample cuvette for SERS and heat output to be monitored simultaneously. We have compared the performance of morphologically complex gold nanoparticles, nanostars (AuNSs) and nanoplates (AuNPLs), which are both well utilized in SERS and photothermal experiments; and measured the SERS activity originating from common Raman reporter analytes 4-mercaptobenzoic acid (MBA) and 1,4-benzenedithiol (BDT). We were able to show that the system effectively measures the thermal output and SERS activity of the particles and can evaluate the effect that multiple irradiation cycles have on the SERS signal.

Journal of Nanotheranostics doi: 10.3390/jnt3020006

Authors: Nikolaos Naziris Costas Demetzos

Lipid nanoparticles (LNPs) are the first approved nanomedicines and the most well-studied class of nanocarriers for drug delivery. Currently, they are in the frontline of the pandemic fight as vaccine formulations and therapeutic products. However, even though they are so well-studied, new materials and new modifications arise every day that can improve their properties. Their dynamic nature, especially the liquid crystal state of membranes, is under constant investigation and it is that which many times leads to their complex biological behavior. In addition, newly discovered biomaterials and nanoparticles that possess promising effects and functionalities, but also toxicity and/or poor pharmacokinetics, can be combined with LNPs to ameliorate their properties. As a result, many promising theranostic applications have emerged during the past decade, proving the huge potential of LNPs in the field. In the present review, we summarize some of the most prominent classes of LNPs for nanotheranostic purposes, and present state-of-the-art research examples, with emphasis on the utilized biomaterials and the functionality that they confer to the resultant supramolecular nanosystems, in relation to diagnostic and therapeutic modalities. Although there has been unprecedented progress in theranostics, the translational gap between the bench and the clinic is undeniable. This issue must be addressed by experts in a coordinated way, in order to fully exploit these nanomedicines for the benefit of the society.

Journal of Nanotheranostics doi: 10.3390/jnt3010005

Authors: Md Walid Akram Hussain Sarah Jahangir Bikona Ghosh Farjana Yesmin Afnan Anis Sabikun Nahar Satil Faizan Anwar Mohammad Harun Rashid

Exosomes are membrane-enveloped nanosized (30–150 nm) extracellular vesicles of endosomal origin produced by almost all cell types and encompass a multitude of functioning biomolecules. Exosomes have been considered crucial players of cell-to-cell communication in physiological and pathological conditions. Accumulating evidence suggests that exosomes can modulate the immune system by delivering a plethora of signals that can either stimulate or suppress immune responses, which have potential applications as immunotherapies for cancer and autoimmune diseases. Here, we discuss the current knowledge about the active biomolecular components of exosomes that contribute to exosomal function in modulating different immune cells and also how these immune cell-derived exosomes play critical roles in immune responses. We further discuss the translational potential of engineered exosomes as immunotherapeutic agents with their advantages over conventional nanocarriers for drug delivery and ongoing clinical trials.

Journal of Nanotheranostics doi: 10.3390/jnt3010004

Authors: Georgios Kareliotis Eleni Chronopoulou Mersini Makropoulou

Plasmonic photothermal and photodynamic therapy (PPTT and PDT, respectively) are two cancer treatments that have the potential to be combined in a synergistic scheme. The aim of this study is to optimize the PPTT treatment part, in order to account for the PDT lack of coverage in the hypoxic tumor volume and in cancer areas laying in deep sites. For the needs of this study, a mouse was modeled, subjected to PDT and its necrotic area was estimated by using the MATLAB software. The same procedure was repeated for PPTT, using COMSOL Multiphysics. PPTT treatment parameters, namely laser power and irradiation time, were optimized in order to achieve the optimum therapeutic effect of the combined scheme. The PDT alone resulted in 54.8% tumor necrosis, covering the upper cancer layers. When the PPTT was also applied, the total necrosis percentage raised up to 99.3%, while all of the surrounding studied organs (skin, heart, lungs and trachea, ribs, liver and spleen) were spared. The optimized values of the PPTT parameters were 550 mW of laser power and 70 s of irradiation time. Hence, the PPTT–PDT combination shows great potential in achieving high levels of tumor necrosis while sparing the healthy tissues.

Journal of Nanotheranostics doi: 10.3390/jnt3010003

Authors: Mohammad Mohtasim Hamid Pial Asahi Tomitaka Nezih Pala Upal Roy

Breast cancer is one of the leading causes of death in the female population worldwide. Standard treatments such as chemotherapy show noticeable results. However, along with killing cancer cells, it causes systemic toxicity and apoptosis of the nearby healthy cells, therefore patients must endure side effects during the treatment process. Implantable drug delivery devices that enhance therapeutic efficacy by allowing localized therapy with programmed or controlled drug release can overcome the shortcomings of conventional treatments. An implantable device can be composed of biopolymer materials, nanocomposite materials, or a combination of both. This review summarizes the recent research and current state-of-the art in these types of implantable devices and gives perspective for future directions.

Journal of Nanotheranostics doi: 10.3390/jnt3010002

Authors: Journal of Nanotheranostics Editorial Office Journal of Nanotheranostics Editorial Office

Rigorous peer reviews are the basis of high-quality academic publishing [...]

Journal of Nanotheranostics doi: 10.3390/jnt3010001

Authors: Loredana Ricciardi Sharmistha Chatterjee Giovanna Palermo Elisabeta I. Szerb Alessia Sanna Francesca Palermo Nicola Pieroni Michela Fratini Roberto Bartolino Alessia Cedola Massimo La Deda Giuseppe Strangi

Glioblastoma multiforme (GBM) is one of the deadliest and most aggressive cancers, remarkably resilient to current therapeutic treatments. Here, we report preliminary in vivo studies of GBM treatments based on photo-nanotherapeutics to activate synergistic killing mechanisms. Core-shell nanoparticles have been weaponized by combining photophysical properties of a new generation PDT agent (Ir(III) complex) with the thermoplasmonic effects of resonant gold nanospheres. In order to investigate the damages induced in GBM treated with these photoactivable nanosystems, we employed X-ray phase-contrast tomography (XPCT). This high-resolution three-dimensional imaging technique highlighted a vast devascularization process by micro-vessels disruption, which is indicative of tumor elimination without relapse.

Journal of Nanotheranostics doi: 10.3390/jnt2040014

Authors: Brandon Z. McDonald Connor C. Gee Forrest M. Kievit

Traumatic brain injury (TBI) is currently the leading cause of injury-related morbidity and mortality worldwide, with an estimated global cost of USD 400 billion annually. Both clinical and preclinical behavioral outcomes associated with TBI are heterogeneous in nature and influenced by the mechanism and frequency of injury. Previous literature has investigated this relationship through the development of animal models and behavioral tasks. However, recent advancements in these methods may provide insight into the translation of therapeutics into a clinical setting. In this review, we characterize various animal models and behavioral tasks to provide guidelines for evaluating the therapeutic efficacy of treatment options in TBI. We provide a brief review into the systems utilized in TBI classification and provide comparisons to the animal models that have been developed. In addition, we discuss the role of behavioral tasks in evaluating outcomes associated with TBI. Our goal is to provide those in the nanotheranostic field a guide for selecting an adequate TBI animal model and behavioral task for assessment of outcomes to increase research in this field.

Journal of Nanotheranostics doi: 10.3390/jnt2040013

Authors: Metka Sluga Saba Battelino Domen Vozel

The diagnostic and therapeutic potential of extracellular vesicles (EVs) has been recognised in many fields of medicine for several years. More recently, it has become a topic of increasing interest in otorhinolaryngology, head and neck surgery (ORL-HNS). With this narrative review, we have aspired to determine different aspects of those nanometrically sized theranostic particles, which seem to have promising potential as biomarkers in some of the most common diseases of the ORL-HNS by being available via less invasive diagnostic methods. At the same time, a better understanding of their activity provides us with new possibilities for developing specific target treatments. So far, most research has been oriented towards the role of EVs in the progression of head and neck cancer, notably head and neck squamous cell cancer. Nonetheless, some of this research has focused on chronic diseases of the ears, nose and paranasal sinuses. However, most research is still in the preclinical or experimental phase. It therefore requires a further and more profound understanding of EV content and behaviour to utilise their nanotheranostic capacities to their fullest potential.

Journal of Nanotheranostics doi: 10.3390/jnt2040012

Authors: Emanuel Sporer Christian B. M. Poulie Sture Lindegren Emma Aneheim Holger Jensen Tom Bäck Paul J. Kempen Andreas Kjaer Matthias M. Herth Andreas I. Jensen

Targeted α-therapy (TAT) can eradicate tumor metastases while limiting overall toxicity. One of the most promising α-particle emitters is astatine-211 (211At). However, 211At-carbon bonds are notoriously unstable in vivo and no chelators are available. This hampers its adoption in TAT. In this study, the stability of 211At on the surface of gold nanoparticles (AuNPs) was investigated. The employed AuNPs had sizes in the 25–50 nm range. Radiolabeling by non-specific surface-adsorption in >99% radiochemical yield was achieved by mixing 211At and AuNPs both before and after polyethylene glycol (PEG) coating. The resulting 211At-AuNPs were first challenged by harsh oxidation with sodium hypochlorite, removing roughly 50% of the attached 211At. Second, incubation in mouse serum followed by a customized stability test, showed a stability of >95% after 4 h in serum. This high stability was further confirmed in an in vivo study, with comparison to a control group of free 211At. The AuNP-associated 211At showed low uptake in stomach and thyroid, which are hallmark organs of uptake of free 211At, combined with long circulation and high liver and spleen uptake, consistent with nanoparticle biodistribution. These results support that gold surface-adsorbed 211At has high biological stability and is a potentially useful delivery system in TAT.