Inorganic-organic hybrid nanoparticles (IOH-NPs) are a promising drug delivery system in oncology due to their high drug-load capacity. In this study, we established a 3D correlative light and electron microscopy (CLEM) workflow that combines confocal fluorescence microscopy (FM) with focused ion beam scanning electron microscopy (FIBSEM) to unambiguously identify and visualize the (sub)cellular uptake and processing of reference fluorescently labeled and zirconium-based IOH-NPs in murine H8N8 breast cancer cells. The 3D-CLEM workflow was set up without the need to add external fiducial markers since image correlation was achieved using lipid droplets as intrinsic correlative landmarks. We observed that all H8N8 breast cancer cells had taken up IOH-NPs after 4 h, and most IOH-NPs were found in clusters within the H8N8 cells. IOH-NPs were internalized by endocytosis within 2 h with increasing cellular concentrations over time and accumulated in endolysosomal vesicles over 24 h, while the overall endolysosomal volume increased between 2 and 6 h after IOH-NP incubation and returned to its original value thereafter, remaining stable for up to 48 h. The 3D-CLEM workflow also revealed changes in the morphology and density of the IOH-NPs inside endolysosomal vesicles, suggesting the dissolution of IOH-NPs after 2 h. We also observed mitochondrial swelling in IOH-NP exposed cells, suggesting stress responses even without drug load. The 3D-CLEM workflow provides new insights into the cellular tracking and processing of IOH-NPs and supports the development of novel nanomedicine strategies.

Myocardial injury (MI) is the primary pathogenic process in many cardiovascular disorders. And inadequate medication targeting, unregulated release, and severe side effects are major issues in treatment. Recently, chitosan-based nano-delivery systems have gained popularity in the precision treatment of cardiovascular diseases due to their high biocompatibility, biodegradability, and ease of chemical modification. These devices can be functionally tuned to respond to the cardiac microenvironment, resulting in tailored drug enrichment and sustained release. In this paper, we provide a systematic assessment of the progress of chitosan and its derivatives in MI treatments, including material design approach, environmental response mechanism, drug loading and release management, and mode of action. It also examines the limitations of clinical translation and predicts future development directions. The study shows that chitosan-based nanosystems have significant potential in regulating inflammation and anti-oxidative stress, as well as promoting vascular neovascularization and myocardial repair.

Epilepsy is a chronic neurological disorder marked by recurrent, unprovoked seizures that can lead to cognitive impairment, psychiatric comorbidities, and reduced quality of life. While seizure control is critical for minimizing long-term neurological harm, conventional antiseizure medications (ASMs) are often hindered by limited brain penetration, systemic toxicity, and pharmacoresistance. Liposomal drug delivery systems offer a promising approach to overcome these limitations by enhancing central nervous system targeting, improving drug solubility and stability, and reducing off-target effects. Recent advances in surface-functionalized and immunoliposomes support site-specific delivery to epileptogenic regions and neuroinflammatory targets, contributing to more precise and better-tolerated therapies. Despite encouraging progress, important challenges remain in formulation optimization, targeting specificity, and clinical translation. Continued refinement of liposomal platforms may significantly advance personalized and effective epilepsy management.

With widespread use of carbon nanotubes (CNTs) in manufacturing, the public is increasingly exposed to these materials being released into the environment, with concerns of potential adverse effects on respiratory health. Studies have demonstrated that exposure to CNTs initiates inflammatory cascades and oxidative stress. CNT inhalation challenge in rodents often produces granulomatous inflammation and lung fibrosis. CNT exposure causes TH2 asthmatic inflammation in animal models. CNTs are implicated in disrupting the delicate balance of extracellular matrix homeostasis, contributing to fibrotic remodeling. Limited mechanistic studies exist but epidemiological data suggest a link between CNT exposure and the development of fibrotic and granulomatous lung diseases. In this review, we will discuss the impact of CNT exposure on the respiratory system and how CNT can be used in modeling lung disease.

Metal nanoparticles (NPs) have emerged as advanced drug delivery systems, combining high therapeutic potential with complex safety considerations. Their unique physicochemical features, including high surface-to-volume ratios, tunable surfaces, and the ability to cross biological barriers, enable applications in targeted drug delivery and theranostics. Gold (Au), silver (Ag), iron oxide (Fe₃O₄), zinc oxide (ZnO), and platinum (Pt) NPs demonstrate outstanding efficacy: AuNPs achieve >90 % drug loading and 3-5× improved tumour targeting, AgNPs show up to 99 % antimicrobial activity, and Fe₃O₄ NPs function as both drug carriers and MRI contrast agents. However, toxicity remains a major hurdle. Reported challenges include dose-dependent cytotoxicity (IC₅₀: 10-40 μg/mL), hepatic retention (30-40 %), oxidative stress (2-10× ROS increase), and immune activation (up to 3-fold cytokine elevation). Safety is governed by physicochemical properties, with <10 nm NPs showing efficient penetration but higher genotoxicity, and cationic surfaces being 2-3× more cytotoxic. Several strategies have been developed to overcome these barriers. PEGylation reduces macrophage uptake by 60-75 % and extends circulation time, biodegradable hybrids reduce long-term accumulation by 70-80 %, and controlled-release systems cut doses by 30-50 % without compromising efficacy. Advances in computational tools, such as machine learning (~87 % predictive accuracy), along with standardized testing (<20 % variability), have accelerated preclinical evaluation by 40-50 %. These improvements contribute to therapeutic indices >10 and Phase I trial success rates of 65-75 %, significantly outperforming first-generation nanocarriers. This review highlights the need for multidisciplinary integration of nanotechnology, toxicology, computational modelling, and regulatory frameworks. With continued innovation, metal NPs hold the potential to revolutionize precision medicine through safer, scalable, and clinically translatable nanoplatforms.

Assays to detect potential biocompatibility issues can play a key role in supporting the development of new technologies such as medical products containing engineered nanomaterials (ENMs). A consensus test method standard on nitric oxide production after cellular ENM exposure was developed and published through ASTM International. In this paper, we describe an evaluation of sources of variability in this method. A significant challenge is ensuring that the protocol contains the necessary control measurements to account for potential issues when testing ENMs. Protocol testing was conducted during draft standard development and post-publication to better understand potential sources of variability such as the impact of insufficient removal of the ENM, the number of cells seeded, the selection of positive control compounds, and the culture techniques of the cells prior to the experiments. Several in-process control measurements were used to monitor the performance of intermediate steps in the assay procedure. Two gold nanoparticles with different surface coatings and nano-sized polystyrene particles were used to demonstrate the applicability of some of the control measurements. This testing revealed which sources of variability were more likely to have a significant impact on the overall assay uncertainty and confirmed the key importance of certain control measurements. These results could also support the standardization of other ENM-related in vitro methods that share similarities in their protocols with the method investigated here. The further development of this method can also support its use to evaluate the potential for substances other than ENMs to induce nitric oxide production.

Nanoparticle delivery systems have been extensively investigated as novel therapeutic strategies to promote drug-resistant disease. These nanoparticle formulations demonstrated improved bioavailability and enhanced tissue targeting. Also, there is growing acceptance of the value of traditional Chinese medicine in fighting disease. In this study, combining the advantages of nanomedicine with the characteristics of the acidic inflammatory microenvironment of atherosclerosis, a nanoplasmonic platform encapsulating the unstable drug Sch was designed for the treatment of atherosclerotic lesions. pH-responsive nanocarriers, an acid-labile material of acetylated β-cyclodextrin (β-CD) (Ac-bCD) were synthesized by chemical modification of β-CD. The resulting nanoparticles loaded with Sch (Sch-NPs) were prepared using a solvent evaporation method. In ApoE mice fed a high-fat diet, Sch-NPs alleviated arterial damage, inhibited lipid metabolism disorders, reduced plaque area, and promoted plaque stability. In addition, Sch-NPs effectively reduced inflammatory infiltration and oxidative stress by modulating the MAPK pathway. Our findings demonstrate the promising applications of pH-responsive nanoparticles loaded with Sch for enhanced disease therapies such as atherosclerosis.

Radioluminescent nanoparticles enable radiotherapy- or X-ray-triggered photodynamic therapy (RT-PDT, also referred to as X-PDT in the literature) using the 5-aminolevulinic acid (ALA) prodrug, thereby overcoming the limited tissue penetration of conventional PDT. However, their therapeutic efficacy remains constrained by poor intratumoral nanoparticle distribution. To address this challenge, we developed collagenase-functionalized calcium tungstate nanoparticles capable of enzymatically degrading the extracellular matrix (ECM) in solid tumors. Micro-CT imaging revealed that collagenase functionalization increased intratumoral nanoparticle distribution by approximately sevenfold. In vivo studies further showed that enhanced penetration improved NP delivery, but that surface-bound maleimide linkers and collagenase partially scavenged reactive oxygen species (ROS), revealing a trade-off between ECM degradation and the quenching of ROS-mediated photodynamic effects. Overall, these findings demonstrates that collagenase-functionalized radioluminescent nanoparticles can effectively overcome stromal barriers in collagen-rich solid tumors, providing a promising strategy for next-generation RT-PDT while underscoring the importance of balancing enzymatic ECM remodeling with preservation of ROS generation.

Iron oxide nanoparticles (IONPs) offer promise for drug delivery and imaging, but their vascular safety requires thorough evaluation. Hydroxyethyl starch (HES) is a clinically used, biocompatible polysaccharide with potential as a nanoparticle coating to improve vascular safety. We synthesized novel hydroxyethyl starch-coated IONPs (IONPs@HES) and assessed their properties and effects on human microvascular endothelial cells (HMEC-1) under basal and inflammatory conditions. IONPs@HES showed magnetite cores, near-neutral charge, and reduced magnetic saturation, supporting biocompatibility. They were efficiently internalized without affecting viability or proliferation (20-500 μg/mL) and did not increase LPS-induced ICAM-1 expression. Autophagic activity, assessed by LC3 immunofluorescence and Cyto-ID flow cytometry, remained unchanged, suggesting preserved autophagic homeostasis. A modest increase in phosphorylated caveolin-1 (p-CAV1) was observed, with no enhancement under LPS stimulation. Co-treatment with indomethacin showed no additive toxicity. These findings support IONPs@HES as a biocompatible nanoplatform suitable for vascular-targeted cancer therapy, meriting further in vivo validation.

Prostate cancer (PCa) remains a major clinical challenge due to limited treatment efficacy, frequent resistance, and high recurrence rates. Given the susceptibility of cancer cells to oxidative stress, reactive oxygen species (ROS)-based strategies offer promising therapeutic potential. Photothermal therapy (PTT) and sonodynamic therapy (SDT) are emerging minimally invasive modalities that exploit nanotechnology to induce localized ROS generation. This review highlights recent advances in ROS-mediated PTT and SDT for PCa, emphasizing nanomaterial design and functionalization to enhance targeting precision, drug delivery, and overcome tumor hypoxia. Combining PTT and SDT with chemotherapy, radiotherapy, or immunotherapy produces synergistic effects, potentially overcoming resistance and eliciting systemic antitumor immunity. Preclinical studies demonstrate effective tumor eradication and immune activation with minimal toxicity, suggesting promise for clinical translation. However, human clinical trials remain scarce, and further translational research is needed before these nanotechnology-based approaches can be integrated into standard PCa treatment.

Mebeverine (MBV) is a clinically approved antispasmodic agent indicated for irritable bowel syndrome (IBS) that functions via direct calcium channel inhibition in gastrointestinal smooth muscle, alleviating spasmodic pain without central anticholinergic effects. Optimal oral delivery mandates protection from gastric acidity (pH ~1.5-3.0) and targeted release in the small intestine (pH ~6.0-7.4) for prompt onset and sustained action. Here, we report a comparative evaluation of tartaric acid-iron(III) metal-organic frameworks (TF-MOFs) functionalized with globulin (TF-GLB) or human serum albumin (TF-HSA), loaded with MBV. TF-GLB-MBV released a higher amount of MBV at 7.4 and 9.0, suggesting unsuitability for neutral and basic environments with a concentration of 2.06 mg (12.73 %) and 3.67 mg (22.69 %) at first 15 min, respectively. For TF-HSA-MBV, the maximum MBV release amounts were 3.58 mg (5.22 %) and 0.9 mg (21.20 %), respectively. This comparative kinetic modeling study reveals that TF-HSA-MBV performs optimally in acidic and alkaline environments, following Higuchi diffusion-based release. Meanwhile, TF-GLB-MBV is more suitable for mildly acidic pH, exhibiting Case II transport, suggesting erosion- or swelling-controlled release-ideal for upper intestinal targeting. However, neither formulation performed optimally at physiological pH (7.4), which may require further formulation optimization. These findings support TF-GLB as a promising oral delivery system for IBS.

Intrathecal drug delivery refers to the direct administration of compounds to cerebrospinal fluid (CSF), which can enhance delivery to the central nervous system (CNS) while minimizing peripheral exposure. Our prior work demonstrated that 100 nm, solid polystyrene nanoparticles surface modified with poly(ethylene glycol) (PEG) distribute within the CNS after intrathecal administration via the cisterna magna route (IT-CM). Here, we focus on comparing nanoparticle fate following administration to IT CM versus lumbar (IT-L) access points. We utilized dynamic a variety of imaging techniques to track the movement of model, Cu-radiolabeled, fluorescent nanoparticles, hypothesizing that the IT-CM route would enable greater brain-localized delivery of nanoparticles when compared with the IT-L route. Spatiotemporal patterns of nanoparticle distribution and clearance were studied through a combination of quantitative positron emission tomography/computer tomography (PET/CT), fluorescent imaging (confocal microscopy), and biodistribution experiments (liquid scintillation counting). These studies revealed that: (1) the IT-CM route yielded greater brain-wide nanoparticle delivery while the IT-L route yielded greater spinal delivery, (2) the IT-CM route resulted in sustained retention of nanoparticles within the CNS and proximal lymphatics while the IT-L route resulted in higher nanoparticle clearance to peripheral organs, and (3) both the IT-CM and IT-L routes resulted in detectable though incomplete parenchymal delivery of nanoparticles, with the majority of signal remaining confined to the subarachnoid space. These findings underscore the pivotal role of intrathecal location in influencing nanoparticle biodistribution and clearance pathways within the CNS, identifying access point as an important design parameter when optimizing nanomedicine for intrathecal drug delivery.

Triple-negative breast cancer (TNBC) frequently develops resistance to radiotherapy, while its metabolic reliance on glucose and glutamine presents new therapeutic targets for radiotherapy sensitization. This study developed a targeted nanoliposome (G/B-Lip-R) co-delivering glucose oxidase (GOD) and buthionine sulfoximine (BSO) to enhance radiotherapy through dual metabolic intervention. GOD catalyzes glucose oxidation to generate hydrogen peroxide (HO) while depleting tumor energy supplies, whereas BSO inhibits glutathione (GSH) synthesis to disrupt redox homeostasis. Their synergistic action significantly elevates intracellular reactive oxygen species (ROS) levels, thereby potentiating radiosensitivity. Both in vitro and in vivo studies demonstrated that G/B-Lip-R effectively targets tumors and significantly improves radiotherapy outcomes. This work innovatively combines nanocarriers with dual metabolic pathway modulation, offering a novel strategy to overcome TNBC radioresistance with important clinical translation potential.

This review delves into the intricacies of Photodynamic Therapy (PDT), focusing on mechanisms such as the accumulation of selective photosensitizers and the generation of Reactive Oxygen Species (ROS). Research is investigating the use of zirconium oxide nanoparticles (ZrO NPs) and their combination with upconversion nanoparticles. The functionalization of ZrO NPs is stressed for targeted drug administration and enhanced therapeutic effects. Addressing PDT challenges, ZrO NPs exhibit potential to enhance treatment accuracy, minimize side effects, and improve overall success. Supported by preclinical and clinical research, zirconium-based PDT emerges as a transformative cancer therapy technique. Integrating ZrO NPs into PDT represents a groundbreaking approach, allowing selective cancer cell targeting and promising improved treatment outcomes and synergies with other modalities. With demonstrated safety and efficacy, ZrO PDT constitutes a vital component in advancing cancer patient outcomes globally.

The blood stage of malaria, where Plasmodium parasites invade red blood cells, accounts for most clinical symptoms and severe complications. However, current drugs and vaccines remain limited by drug resistance, toxicity, poor stability, and reduced overall efficacy. This review aimed to synthesize evidence on nanotechnology-based delivery systems for improving targeting specificity, enhancing drug and antigen stability, and optimizing therapeutic outcomes. Forty (40) studies from 2005 to 2025 were systematically analyzed, focusing on lipid, polymeric, inorganic, and protein-based nanoparticles targeting the blood stage. Results showed that functionalized nanocarriers with ligands targeting infected red blood cells significantly enhanced drug efficacy and reduced systemic toxicity. In vaccine development, nanoparticles used as antigen carriers elicited strong immune responses, achieving up to 83.3 % survival in in vivo preclinical models. Despite these promising outcomes, challenges such as scalable production, clinical translation, and regulatory approval persist. Overall, the findings highlight nanomedicine's transformative potential for malaria treatment and prevention.

The beneficial physical, chemical, and biological properties of proteins make them useful building blocks in the construction of biomedicals and nanomaterials. There are various biomaterials to develop inventive drug delivery systems ranging from simple to complex proteins which can be more efficient for patients undergoing surgical procedures. In the line of this article, the definition of medicine via proteins is based on complex bioengineering systems that mix tailored biomaterials with molecular algorithms to form controlled bioactive nanosystems. Among biomaterials, proteins are unique, because they can be found directly in nature, which qualify them easy for use, especially in surgical procedures. This article is aimed at describing their origin, structural properties, functions characteristics of interest in biology, and activity as drug delivery systems. Their native form and form of biomaterials i.e., hydrogels, scaffolds, membranes, fibers, and nanoparticles are examined. The article discusses novel designed nanoarchitectures aimed to solve long lasting problems in drug delivery like poor drug solubility, low bioavailability, and encapsulation of active pharmaceutical ingredients (APIs). The most important innovations are systems that respond to stimuli, mucoadhesive and mucus penetrating structures, lymphatic-targeting designs, and carriers that respond to environmental changes. Moreover, the article outlines the therapeutic uses of biomaterials based on proteins in tissue engineering (bone, cartilage, skin, cardiac, and neural tissue engineering), cancer treatment, diabetes, gene therapy, and in the treatment of inflammatory and chronically symptomatic disorders. Each part is arranged to minimize overlap and highlight functional distinctiveness to provide a cohesive design that integrates structure, function, and use. The review ends with the discussion of the existing gaps and the proposed pathways for future investigations which could facilitate the clinical translation of the work. This work serves as a stimulus toward the rational conception of protein-based materials and designed nanocarriers which are structurally tailored and application-driven, increasing their impact in the fields of drug delivery and regenerative medicine.

Nanotechnology-based approaches (NBA) can improve tumor diagnosis and treatment. Thus, zebrafish (Danio rerio) emerge as a model system to investigate antitumoral effects, biodistribution and mechanism of action of nanomaterials (NMs). The current study aimed to summarize and critically analyze the literature concerning the use of zebrafish as an in vivo model for assessing the NBA in diagnosis, therapy and theranostics of cancer. Revised data (n = 95) showed an increasing number of publications in recent years. The main study approach was therapeutic (83.16 %), while diagnosis and theranostics represented 9.47 % and 7.37 %, respectively. 95.8 % used the embryo-larval stage of zebrafish. The most studied NM was the nanoparticles (NPs). Breast cancer, liver and melanoma were the tumors most studied. Overall, NMs can reduce chemotherapeutic drug toxicity, inhibit tumor growth, metastasis and angiogenesis, also promote tumor imaging and tracking. Zebrafish is a suitable emerging model system in cancer nanomedicine research.

This study aims to investigate the anticancer properties of capsaicin, the active substance of red pepper, in different concentrations (2 %, 6 %, and 10 %) by chitosan and polyvinyl alcohol nanofiber substrate, against the K562 leukemia cell line. For this purpose, chitosan (Cs) and polyvinyl alcohol (PVA) polymers were used to produce nanofibers with a 20/80 ratio by electrospinning, with capsaicin serving as the anticancer drug. The properties of the fabricated nanofibers were evaluated by field emission scanning electron microscopy. Also, gold nanoparticles were used to analyze and compare its effectiveness against the K562 cancer cell line. This cell line was prepared from Pasteur cell bank and cultured in DMEM medium. Subsequently, the anticancer effect of synthetic nanofibers in different concentrations was assessed by performing survival test, apoptosis by annexin and propidium iodide staining, and cell scratch assay. The electron microscopy study demonstrated the uniformity and purity of the nanofiber structure. The results showed that capsaicin, dose-dependently, reduced the viability of K562 cells after 72 h (P < 0.01). The apoptotic assay also indicated that the induction of apoptosis significantly increased by PVA/Cs/Caps(2 %) and PVA/Cs/Au(5 %)/Caps(10 %) compounds in the studied cell line (P < 0.0001). Furthermore, scratch assay at 24, 48, and 72 h demonstrated that the mentioned compounds possess anti-migration potential, particularly at 48 h. Our results suggest that capsaicin in nanofiber substrate can show anticancer properties against the K562 leukemia cell line. Therefore, this compound can be considered a potential candidate for the treatment of leukemia.

Development of a transdermal drug delivery system must overcome the limited efficacy and reliability of current skin penetration methods. This study examined whether synthetic chromatin conjugated with the cell-penetrating peptide gH625 could traverse the epidermal barrier while maintaining cargo bioactivity. gH625-linked histone H2A assembled into chromatin was used to deliver DNA and peptides without penetration enhancers. gH625-chromatin increased cellular penetration by 150 % compared with wild-type chromatin. Ex vivo porcine and in vivo mouse skin models demonstrated enhanced penetration depth up to 242 μm within 24 h, with signals confined to the dermis, indicating safe localized delivery. Epidermal growth factor (EGF) displayed at the histone H2B C-terminus maintained activity equivalent to free EGF, promoting cell growth, elevated COL1A1 secretion, and accelerated wound closure. These findings establish a chromatin-based nanoplatform for non-invasive transdermal delivery of bioactive macromolecules, filling a key gap in skin-targeted biotherapeutic delivery.