Search Results (361)

Nanobiochar has attracted increasing attention as a redox-active carbon nanomaterial with potential applications beyond its traditional roles in environmental remediation and adsorption technologies. When integrated into hydrogel matrices, nanobiochar may provide a unique combination of physicochemical and biological functionalities, including reactive oxygen species (ROS) modulation, antimicrobial activity, high adsorption capacity, and localized therapeutic delivery. Such properties are particularly relevant to emerging wound-healing and regenerative medicine applications; however, the biological mechanisms governing the performance of nanobiochar–hydrogel systems remain poorly understood. Because direct studies on nanobiochar–hydrogel therapeutic systems remain scarce, this review integrates evidence from the limited nanobiochar literature together with evidence from studies on conventional biochar, hydrogel biomaterials, and related carbon nanomaterial to critically evaluate emerging biological mechanisms and identify future research priorities. This review combines bibliometric analysis with mechanistic evaluation to assess the potential of nanobiochar–hydrogel systems as therapeutic biomaterials while highlighting critical knowledge gaps limiting their development. Bibliometric findings reveal that research on biochar–hydrogel composites is dominated by environmental remediation, adsorption processes, and material characterization, whereas investigations addressing biological responses and therapeutic functionality remain limited. Building upon these observations, this review examines nanobiochar surface chemistry, electron transfer behavior, and redox-active properties that may influence ROS regulation at biological interfaces. Particular emphasis is placed on biointerface interactions, including protein adsorption, protein corona formation, cellular uptake pathways, and the influence of hydrogel-mediated exposure on biological responses. The review further evaluates potential antimicrobial mechanisms, redox-sensitive signaling pathways, cytocompatibility assessment strategies, and the behavior of nanobiochar-containing systems under physiologically relevant conditions. Current evidence indicates a strong reliance on chemical antioxidant assays and short-term viability measurements, while mechanistic investigations involving intracellular ROS regulation, inflammatory signaling, mitochondrial function, and gene expression responses remain scarce. Collectively, the literature discussed in this article highlights the substantial gap between material development and biological validation and provides a framework for future studies aimed at evaluating the suitability of nanobiochar–hydrogel systems for wound-healing and regenerative applications. Full article

Nanoplastics (NPs; ≤1 µm) have been detected in human placenta, blood, lung, atherosclerotic plaque, testis, semen, olfactory bulb, and brain, shifting the field from environmental description toward mechanistic interrogation of barrier crossing. This review synthesises current evidence on NP translocation across the intestinal epithelium, the blood–brain barrier (BBB) and the placental syncytiotrophoblast. We distinguish four evidence categories throughout the review: detection, association, mechanism, and causality. We also apply model-system labels (in silico, in vitro, ex vivo, animal, and human) to every mechanistic claim, so that the strength of each statement can be read off directly. Most current studies use pristine polystyrene nanoplastics at concentrations 3–6 orders of magnitude above plausible human exposure, so the mechanistic conclusions below are hypothesis-generating for human disease rather than definitive. We propose a working conceptual framework—corona-driven barrier selectivity (CDBS)—in which the particle–corona–surface complex, rather than the bare polymer, is hypothesised to dictate which receptor and transport machinery (TfR1, LRP1, FcRn, P-gp/BCRP, caveolae) each barrier engages. CDBS is offered as a hypothesis-stage organising tool requiring experimental validation, not as an established mechanism. We outline reported transport modes, including clathrin- and caveolin-mediated endocytosis, paracellular leakage via ROS-induced tight-junction disassembly, receptor-mediated transcytosis, and the candidate olfactory route. We emphasise that pristine polystyrene-bead doses commonly exceed plausible human exposure by 3–6 orders of magnitude, that detection methods underestimate sub-micrometre particles, and that causal links between NPs and human disease remain hypothesis-generating. A research agenda built on weathered reference materials, microphysiological systems, and integrative human biomarker science is proposed. Full article

Nanoparticles combining gold and iron oxide are promising for a wide range of biomedical applications, including photothermal therapy, radiotherapy enhancement, drug delivery, and diagnostic imaging. However, their long-term biodistribution and safety profile remain largely unexplored. Here, we synthesized Fe₃O₄@AuNP core–satellite nanoparticles (Fe₃O₄@AuNPs) using femtosecond laser ablation, functionalized them with 15 kDa polyethylene glycol (PEG), and characterized them using a panel of physicochemical techniques. Healthy C57BL/6 mice received an intravenous injection of Fe₃O₄@AuNPs at 730 mg Au/kg and 82 mg Fe/kg, respectively. Biodistribution was monitored by computed tomography (CT) and magnetic resonance imaging (MRI) over 12 months, after which gold and iron concentrations were measured ex vivo, and long-term toxicity was assessed via histology and blood biochemistry. Nanoparticles accumulated predominantly in the liver and spleen. Quantitative analysis of CT images revealed a gradual decrease in gold content, while MRI showed a progressive reduction in negative contrast in the liver between 6 and 12 months, suggesting possible changes in the Fe₃O₄ core structure. Over the one-year observation period, no differences in behavior or body weight gain were detected between the treated and control groups. Histological examination revealed no pathological changes other than mild age-related alterations. These findings provide a baseline for the long-term behavior of laser-ablated core–satellite Fe₃O₄@AuNPs, which is essential for their further development in diagnostic and theranostic applications. Full article

Biogenic metal nanoparticles are naturally covered with the phytochemical corona, which includes plant-derived metabolites. Emerging evidence suggests that the phytochemical corona, together with the intrinsic properties of the metallic core, contributes significantly to the biological identity, therapeutic behavior, and safety profile of biogenic nanoparticles. In this review, we go beyond the traditional view of plant extracts as reducing and capping agents to the phytochemical corona as a programmable nano–bio interface. Green synthesis from Indian flora has potential that can yield coronas rich in flavonoids, polyphenols, terpenoids, and alkaloids. Each corona composition contributes to different physicochemical properties, such as cellular interactions and downstream effects on reactive oxygen species, endocytic uptake and signaling pathways (p53, AKT, MAPK). When in contact with biological fluids, the corona adsorbs host proteins, giving rise to a hybrid interface that further influences the therapeutic outcome. The corona composition directly contributes to the biological activities of these nanoparticles: for example, anticancer, antimicrobial, antioxidant, and antiparasitic. The corona offers intrinsic targeting, stimuli-responsive release and improved stability for drug delivery. Toxicity and safety assessment shows dose-dependent effects, organ accumulation and long-term concerns for which standardized testing is needed. Translational challenges include: reproducibility, seasonal and geographic phytochemical variation, variability in extraction methods, scalability, shelf life and regulatory ambiguity. Future directions include Artificial intelligence (AI)-driven phytosynthesis, precision nanomedicine, nano–bio interface engineering, multi-omics integration, exploration of endangered Indian flora, and digital twin modeling. This review provides a roadmap for engineering phytochemical coronas as precision nanomedicine platforms by shifting the focus from core to corona and from empirical recipes to predictive design. It positions biogenic nanoparticles not only as eco-friendly alternatives, but as programmable, superior therapeutics for cancer and drug-resistant infections. Full article

Artificial intelligence (AI) is increasingly influencing nanopharmaceutical development by supporting the transition from empirical formulation screening toward predictive, data-driven, and translationally oriented design. Nanocarrier-based therapeutics are governed by nonlinear relationships among material composition, physicochemical attributes, manufacturing parameters, biological identity, pharmacokinetics, toxicity, and therapeutic performance. In this review, we examine how AI can contribute to nanopharmaceutical development from predictive formulation design to clinical translation. We synthesize current applications of machine learning, deep learning, physics-informed modeling, hybrid mechanistic–AI approaches, and automated optimization workflows, with emphasis on critical quality attribute modeling, multi-objective optimization, design of experiments, quality-by-design, process analytical technology, digital twins, and continuous manufacturing. We also discuss applications involving nano–bio interactions, pharmacokinetics, toxicity, immunogenicity, and precision nanomedicine. AI-based approaches can support rational nanocarrier design, identify nonlinear formulation–property relationships, guide optimization, improve process understanding, and integrate heterogeneous experimental, biological, and manufacturing datasets across diverse nanopharmaceutical platforms. These methods are particularly relevant for modeling protein corona formation, cellular uptake, intracellular trafficking, biodistribution, pharmacokinetics, toxicity, immunogenicity, and patient-specific responses. However, translational implementation remains limited by fragmented datasets, inconsistent reporting standards, limited interpretability, insufficient external validation, uncertain predictions, poorly defined applicability domains, and evolving regulatory expectations for adaptive computational models. Overall, AI should be viewed not only as an optimization tool, but also as a translational framework connecting formulation science, biological prediction, manufacturing control, and clinical implementation. Future progress will depend on standardized data infrastructures, explainable and externally validated models, uncertainty quantification, applicability-domain definition, hybrid mechanistic–AI frameworks, regulatory-ready documentation, and clinically relevant case studies. Full article

Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with poor outcomes in advanced stages and significant limitations in current chemotherapy regimens due to systemic toxicity. Extracellular vesicles (EVs) have emerged as promising natural drug delivery vehicles, offering the potential for targeted, less toxic therapies. This study investigates the feasibility of using autologous, patient-derived EVs as a delivery system for the chemotherapeutic agent doxorubicin, focusing on how disease stage and the EV protein corona influence loading and delivery efficiency. Methods: EVs were isolated from plasma and tissue samples of CRC patients at different disease stages, as well as from healthy controls, demonstrating successful isolation and characterisation of EVs, with distinct profiles across different sources. Results: Doxorubicin loading into EVs was significantly higher in CRC patient-derived EVs compared to healthy controls, and tissue-derived EVs yielded higher quantities of drug-loaded particles. Delivery of doxorubicin-loaded EVs to recipient CRC cell lines (SW480 and SW620) revealed that disease stage impacts both EV uptake and drug delivery, with late-stage EVs showing reduced uptake and delivery efficiency. The protein corona, known to coat circulating EVs, was found to influence drug loading and delivery. Pre-treatment of cell line-derived EVs with plasma proteins enhanced EV uptake but reduced doxorubicin loading and subsequent delivery, particularly when using plasma from healthy volunteers. Conclusions: These findings underscore the importance of EV source and protein corona composition in optimising drug delivery strategies. Our results suggest that autologous, patient-derived EVs hold potential as a targeted drug delivery system for CRC, but highlight the need for further optimisation of EV isolation, loading methods, and understanding of how disease progression affects EV functionality. This approach could ultimately reduce systemic toxicity and improve therapeutic outcomes for CRC patients. Full article

Despite extensive research, formation and properties of protein corona (PC) remain largely unknown. The composition and properties of PC are unique to each particle type. Our research focuses on multilevel nanoconstructs (MLNCs) containing a core (AuNP coated with oligonucleotide) encapsulated in lipid envelope (LE). We are developing particles of this type as nucleic acid delivery systems and platforms for studying PC on lipid surfaces. The goal of this work is to optimize the assembly of MLNCs with a negatively charged LE encapsulating a negatively charged core. Magnesium ions successfully acted as electrostatic bridges between like-charged components to facilitate self-assembly. The resulting particles were characterized using DLS (hydrodynamic diameter of ~36 nm) and TEM, which revealed stable LE. However, we encountered a critical issue: mechanical strength of the phosphatidylcholine/phosphatidic acid/cholesterol envelope proved to be highly sensitive to centrifugation forces and interactions with proteins. Incubation with albumin destabilized the LE, resulting in core release. In contrast, exposure to serum maintained the integrity of LE, allowing isolation of MLNC particles bearing PC. These results demonstrate that the assembly protocol can be adapted to negatively charged lipid compositions. However, stability of MLNCs during isolation is strictly dependent on medium protein composition. Thus, MLNCs represent a valuable platform for studying the interactions of LE with the PC. Full article

This review offers an in-depth look at the diagnostic and therapeutic potential of MNPs as superparamagnetic and high-surface-area-to-volume entities, considering their applications in MRI, magnetic hyperthermia, and targeted drug delivery. Based on an integrative approach, which includes systematic searches in 3 main bibliographic databases, 870 articles, semantic network analysis, Retrieval-Augmented Generation (RAG), and gap classification (Miles’ taxonomy), our analysis identifies a constant gap between lab performances and in vivo applications, described through eight critical challenges. The development of MNP-based biotechnologies is largely hindered by open issues in terms of safety, standardization, and control of the nanobio interface, mainly incomplete physicochemical characterization and poor methodological harmonization, because the high sensitivity of MNPs to synthesis routes and scale is a major bottleneck for GMP-compatible translation. Moreover, the analysis of in vivo data suggests that, on average, less than 1% of the injected dose accumulates in solid tumors, whereas a substantial fraction is diverted to non-target organs, particularly those associated with the mononuclear phagocyte system, reinforcing concerns regarding off-target sequestration, incomplete clearance, and long-term safety. Other critical challenges include complex interactions with biofluids, lack of unifying conceptual frameworks, limited experimental validation, underexploited methodological integration, and geographical and biological biases. Consequently, successfully overcoming these challenges will require the early and deliberate integration of rigorous materials engineering, mechanistic biological insight, and application-oriented validation for robust, reproducible, and translatable magnetic nanoplatforms. Full article

The biological effects of nanoparticles (NPs) form the basis of their safety assessments and biomedical applications. However, most related studies have focused on exposing biological systems such as cells and animals to individual NPs. This is far removed from real-world environmental exposure and biomedical application scenarios involving NPs. In practice, NPs often coexist with other types of NPs or the same type of NPs of different sizes. Interactions between mixed NPs can alter their dispersion states and biological behaviors, thereby influencing their cellular internalization, distribution, and ultimately determining their toxicity outcomes. In this review, we summarize the research progress and current understanding of the biological effects of mixed NPs. We focus on how co-exposure influences the uptake/absorption, fate, and toxicity of NPs in cells and animals. Co-exposure results in an increased, decreased, or unaffected cellular uptake of NPs by altering their dispersion states and protein corona in biological media, and thus their uptake routes. Cytotoxicity of mixed NPs exhibits patterns of synergistic, antagonistic, or additive effects, and is not always positively correlated with the intracellular contents of the NPs, highlighting the complexity of the response of biological systems to NP co-exposure. In vivo evidence further indicates that co-exposure to NPs can result in alterations in the absorption efficiency, tissue distribution, and clearance of the NPs, and thus their overall toxicity. Finally, we discuss the limitations of the current research on the biological response to mixed NPs, and propose key challenges and future directions towards a more standardized, mechanism-based assessment of NP mixtures. Full article

Biocorona (BC) formation is a critical determinant of nanoparticle (NP) biological identity and downstream interactions, yet lipid association within BCs remains comparatively understudied relative to proteins, despite its potential relevance to NP stability, biodistribution, cellular interactions, and clearance. A more complete understanding of NP–lipid interactions is essential for optimizing NP-based therapies and supporting their safe clinical translation. In this study, we evaluated how serum concentration, biological sex, and NP size influence lipid association with iron oxide (Fe₃O₄) NP BCs. Lipids associated with 50 or 100 nm Fe₃O₄ NPs were characterized following incubation in male or female human serum across increasing serum concentrations of 5%, 10%, 25%, 50%, or 75% (v/v). Increasing serum concentration promoted greater lipid association and increased BC complexity, with higher serum conditions yielding more compositionally diverse lipid coronas. BCs formed on 50 nm Fe₃O₄ NPs consistently contained more lipid species than those formed on 100 nm Fe₃O₄ NPs, indicating pronounced size-dependent differences in lipid recruitment. BCs formed in male serum also contained more lipid species and a greater number of unique lipids than corresponding female BCs, demonstrating that biological sex significantly influenced both lipid composition and abundance within the BC. Rank-based comparisons further indicated that lipid association was governed not only by serum abundance but also by selective binding behaviors. Together, these findings demonstrate that lipid corona formation is strongly shaped by both the biofluid environment and NP design variables, emphasizing the importance of considering lipid coronas in NP design and evaluation, particularly for applications in drug delivery, nanomedicine, and precision diagnostics. Full article

This review demonstrates that the diagnostic and prognostic significance of glial fibrillary acidic protein (GFAP) is not limited to its use as a marker of astrocytic damage but should also be considered in the context of the diversity of GFAP isoforms, their heterogeneous tissue-specific expression and their pronounced association with extracellular vesicles (EVs). The data presented in this review indicate that GFAP-positive (GFAP+) EVs possess broad clinical relevance in both acute and chronic pathologies of the nervous system, including ischemic stroke, traumatic brain injury, glioblastoma, and potentially diabetic and drug-induced polyneuropathy. Particular attention is given to the critical analysis of methodological approaches for studying GFAP+ EVs, including discussion of their proposed biogenesis, mechanisms of intravesicular incorporation of cytoskeletal fragments, and the hypothetical sorption of GFAP within the vesicular protein corona. A principal conclusion of this work is that, despite the high translational potential of GFAP+ vesicles as a novel liquid biopsy platform, further implementation of this approach in clinical practice will require standardization of EV isolation protocols, harmonization of phenotyping methodologies in accordance with MISEV 2023 recommendations, and large-scale prospective studies aimed at validating the biological nature, origin, and clinical reproducibility of identified GFAP-associated vesicular subpopulations. Full article

In response to the plastic pollution crisis, bioplastics emerged as a sustainable alternative. However, low degradation rate and abiotic decomposition generate micro- and nanoplastics. These particles enter the food chain, establishing oral intake as a key route of human exposure. This review gathered studies on the biotransformation of bioplastics in the gastrointestinal tract and on their toxicity in human cells and murine models. Most studies focused on polylactic acid particles due to widespread use in food packaging. Under simulated gastrointestinal conditions in vitro, particles were modulated, resulting in cavity and pore formation, fragmentation, lipase competition, protein corona formation, and alterations in the gut microbiota (including Selenomonadaceae, Bifidobacterium, and Prevotellaceae). Also, particle breakdown increases surface area, enhancing interactions with biomolecules and causing higher in vitro and in vivo toxicity. Indeed, pro-inflammatory cytokine secretion, oxidative stress induction, and redox imbalance were found in both models. In mice, alterations in gut microbiota involving Bacillales indirectly mediated hepatotoxicity, leading to uric acid and triglyceride accumulation. Furthermore, microbiota adaptation over time was suggested with an increase in microorganisms and the potential conversion of L-lactic into harmful D-lactic acid. Despite limited studies, this review highlighted that ingested bioplastic-derived micro- and nanoplastics can lead to toxic effects. Full article

Silver nanoparticles (AgNPs) have gained significant interest across various areas arising from their multifunctional mechanisms. Biomedical applications are one of the areas where the therapeutic and diagnostic potential of AgNPs are highlighted. Considering the expansion of biomedical use of AgNPs, nervous system-based applications, including neuroimaging, neural implant coatings and development of neural tissue-targeted drug delivery systems are some of the potential applications of AgNPs in the current research. However, growing interest in these nervous system related applications and the limited regenerative capacity of neural tissues make it essential to carefully evaluate the potential neurotoxic effects of AgNPs. AgNP-induced responses in neural tissues may differ according to key physicochemical and exposure-related parameters, specifically particle size, shape, surface chemistry, coating properties, protein corona formation, exposure route, dose, and duration. Among the possible mechanisms that may contribute to these responses are blood–brain barrier (BBB) disruption, mitochondrial dysfunction and oxidative stress, neuroinflammation and glial activation, and cell death processes such as apoptosis, autophagy, and ferroptosis. In this review, in the context of the potential neurotoxic effects of AgNPs on the nervous system, the main parameters that determine AgNP neurotoxicity and the possible mechanisms involved are examined in detail, where recent scientific developments in this field are evaluated based on current in vitro and in vivo studies. Full article

Over the past decade, antibacterial materials have become a promising strategy to address both antibiotic-resistant and biomaterial-associated infections in clinical settings. Despite substantial progress, a gap remains between promising antibacterial performance in vitro and limited therapeutic outcomes in vivo. Herein, we present a mechanistic framework for understanding formulation-dependent antibacterial performance across five representative formulation architectures: nanoparticle-based systems, nanofibrous scaffolds, hydrogel matrices, surface coatings, and vesicular or microencapsulated carriers. We impart how structural organization and delivery dynamics regulate antibacterial mechanisms such as contact-mediated killing, controlled therapeutic release, and reactive oxygen species (ROS) generation and discuss their context-dependent suitability for diverse infection scenarios; these include acute wound infections, biofilm-associated implant infections, and chronic infected wounds. Particular emphasis is placed on factors contributing to the frequent failure of high in vitro log reduction efficacy translating into clinical success, including protein corona formation, biological barrier penetration, and dynamic host–pathogen interactions. Finally, we propose a comparative formulation-selection framework based on infection type, tissue environment, and therapeutic objectives to guide the rational design of next-generation antibacterial materials. This perspective bridges the gap between material innovation and clinical translation by highlighting formulation architecture as a central determinant of antibacterial performance in biomedical applications. Full article

This review surveys how nanoparticles and biomolecular nanosized structures interact with model membrane systems, and how these interfacial processes govern their performance in drug and gene delivery, antimicrobial strategies, biosensing, and nanotoxicology. The nanostructures covered include polymeric nanoparticles, lipid-based carriers, peptide nanostructures, dendrimers, and multifunctional hybrids. Model membranes span Langmuir monolayers, supported lipid bilayers, vesicles/liposomes across sizes, and emerging hybrid or asymmetric constructs that better approximate native complexity. Mechanistically, interactions follow recurrent routes—surface adsorption, bilayer insertion, pore formation, and lipid extraction/reorganization—regulated by particle size, morphology, charge, ligand architecture, and lipophilicity, in conjunction with membrane composition, phase state, curvature, and asymmetry. A multiscale toolkit links structure, mechanics, and dynamics: Langmuir troughs and Brewster Angle Microscopy map thermodynamics and mesoscale morphology; atomic force microscopy and quartz crystal microbalance with dissipation resolve nanoscale topography and viscoelasticity; fluorescence microscopy/spectroscopy reports on localization and packing; neutron and X-ray reflectometry quantify vertical structure; molecular dynamics provides atomistic pathways and design hypotheses. Historically, the field advanced from early monolayers and bilayers, through the fluid mosaic model, to raft microdomains and modern biomimetic systems, enabling increasingly realistic experiments. Key advances include cross-method integration linking experimental observations with image-based computational models; persistent debates concern the translation from simplified models to living membranes, the role of dynamic coronas, and scale/force-field limits in simulations. Future efforts should prioritize hybrid models incorporating proteins and asymmetric lipidomes, standardized reporting and reference systems, rigorous coupling of experiments with calibrated simulations and machine learning, and alignment with safety-by-design and regulatory expectations, thereby shifting interfacial measurements from descriptive observation to predictive design rules. Full article