Journal of Nanotheranostics

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article