Journal of Nanotheranostics

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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, CeO_2, 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. Full article

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. Full article

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. Full article