International Journal Of Nanomedicine[JOURNAL]
Sun
200 papers
Gestational Intranasal Exposure to Silicon Dioxide Nanoparticles in Rats.
Jeong JS, Kim D, Kim W … +12 more , Kim SY, Lee SY, Park JD, Wi IS, Park C, Kim JH, Jeong W, Suh HN, Kang MS, Kim IH, Kim SH, Lee J
Int J Nanomedicine · 2026 · PMID 42305692 · Full text
BACKGROUND: Silicon dioxide nanoparticles (SiONPs) are among the most widely manufactured nanomaterials, used in diverse industrial, pharmaceutical, and consumer products. Although the respiratory tract represents one of...
BACKGROUND: Silicon dioxide nanoparticles (SiONPs) are among the most widely manufactured nanomaterials, used in diverse industrial, pharmaceutical, and consumer products. Although the respiratory tract represents one of the major routes of human exposure, the potential reproductive and developmental toxicity of SiONPs via respiratory exposure remains poorly characterized. METHODS: This study investigated the maternal and developmental toxicity of SiONPs in pregnant Sprague-Dawley rats. Pregnant animals were intranasally administered SiONPs once daily during gestation day (GD) 6 to 20 at doses of 0, 2, 6, and 20 mg/animal, followed by caesarean section on GD 21. RESULTS: Treatment-related changes were observed in the respiratory tract, appearing as mild inflammatory and regenerative alterations. No mortality or systemic maternal toxicity was observed, and evaluation of caesarean section parameters and fetal morphology demonstrated no evidence of adverse developmental effects. CONCLUSION: Repeated intranasal exposure to SiONPs during pregnancy induced localized histopathological changes in the respiratory tract, with no evidence of systemic maternal or embryo-fetal toxicity at the assessed endpoints under the present experimental conditions. These findings provide experimental data relevant to the assessment of respiratory exposure to SiONPs during pregnancy; however, further studies are warranted considering the diverse properties of nanoparticles and the potential for varied exposure scenarios.
From Laboratory to Clinic: Translational Medicine Paradigm of Polymyxin B Nanopreparations for Overcoming Drug-Resistant Bacterial Infections.
Li N, Cao Y, Li M … +3 more , Zheng D, Zhong W, Yang C
Int J Nanomedicine · 2026 · PMID 42299345 · Full text
The global prevalence of multidrug-resistant (MDR) Gram-negative bacterial infections has posed a severe threat to public health security. As the "last line of defense" antibiotic against such infections, polymyxin B is...
The global prevalence of multidrug-resistant (MDR) Gram-negative bacterial infections has posed a severe threat to public health security. As the "last line of defense" antibiotic against such infections, polymyxin B is severely limited in clinical application by dose-dependent nephrotoxicity (25-50% incidence), neurotoxicity, and the global spread of mcr-mediated resistance. Nanotechnology overcomes these limitations through three key mechanisms: (1) targeted enrichment at infection sites to reduce systemic exposure; (2) controlled drug release to minimize peak concentration-related toxicity; and (3) synergistic co-delivery to reverse bacterial resistance. This review systematically summarizes the design principles and research progress of polymyxin B nanopreparations, focuses on analyzing the core issues encountered in their clinical translation, including insufficient biosafety verification, limited targeted delivery efficiency, immature large-scale production technology, and lack of drug resistance prevention and control systems. However, these nanopreparations still face critical translational challenges including unclear long-term toxicity mechanisms, poor biofilm penetration, and lack of standardized quality control. Combined with the latest research findings, targeted solutions are proposed, including optimization of carrier material biocompatibility, construction of intelligent responsive targeting systems, establishment of standardized production processes, and development of multi-dimensional drug resistance monitoring strategies. This review aims to provide theoretical support and technical guidance for the clinical translation of polymyxin B nanopreparations, promote their clinical application in the treatment of MDR bacterial infections, and offer a reference paradigm for the development of novel antibacterial preparations.
Nanoengineered Macrophages for in vivo Three-Dimensional Photoacoustic Imaging and Immunotherapy of Acute Lung Injury.
Tang Y, Liang C, Meng F … +3 more , Yin W, He F, Zhang J
Int J Nanomedicine · 2026 · PMID 42299344 · Full text
BACKGROUND: Acute lung injury (ALI) is a life-threatening condition lacking effective real-time monitoring and targeted therapeutic strategies. Cell-based drug delivery systems offer promise but are limited by the inabil...
BACKGROUND: Acute lung injury (ALI) is a life-threatening condition lacking effective real-time monitoring and targeted therapeutic strategies. Cell-based drug delivery systems offer promise but are limited by the inability to track their in vivo distribution and therapeutic response. METHODS: Macrophages were engineered to carry aluminum hydroxide-stabilized Tocilizumab (Alum/Toc) and labeled with indocyanine green (ICG) for photoacoustic (PA) imaging. The resulting platform (MΦ/ICG@Alum/Toc) was intravenously administered to Lipopolysaccharides (LPS)-induced ALI mice. Photoacoustic computed tomography (PACT) was used to monitor the dynamic recruitment, pulmonary accumulation, and clearance of the engineered cells over 48 h. Therapeutic efficacy was evaluated by histopathology and lung wet/dry ratio, and biosafety was assessed in major organs. RESULTS: PACT enabled non-invasive, high-resolution tracking of nanoengineered macrophages, revealing rapid homing to inflamed lungs within 6 h, peak accumulation at 24 h, and subsequent hepatic clearance. Three-dimensional (3D) volumetric analysis confirmed targeted pulmonary delivery with minimal off-target distribution. The MΦ/ICG@Alum/Toc platform significantly reduced alveolar edema, inflammatory infiltration, and histopathological scores compared to free Toc, demonstrating superior therapeutic efficacy with excellent biocompatibility. CONCLUSION: This study establishes PACT as a powerful tool for guiding and monitoring cell-based therapies in real time. The nanoengineered macrophage platform offers a clinically translatable strategy for precision immunotherapy of ALI, with potential applications in other inflammatory diseases.
Advances in Tetrahedral Framework Nucleic Acids (tFNAs) for Lung Injury Repair: Mechanisms, Therapeutic Applications, and Future Directions.
Song J, Chen X, Hou Q … +2 more , Zhao P, Zu X
Int J Nanomedicine · 2026 · PMID 42299343 · Full text
Lung injury is a pathological condition caused by a range of direct or indirect factors that disrupt the alveolar-capillary barrier and damage the structure of the lung parenchyma, leading to impaired gas exchange and co...
Lung injury is a pathological condition caused by a range of direct or indirect factors that disrupt the alveolar-capillary barrier and damage the structure of the lung parenchyma, leading to impaired gas exchange and compromised respiratory function. Lung injury shows a high incidence worldwide and remains associated with high mortality, and safe, effective, and reliable therapeutic strategies for this condition are still lacking. Tetrahedral framework nucleic acids (tFNAs) represent a significant advancement in nucleic acid nanotechnology. As novel therapeutic agents and nanocarriers, tFNAs possess an intrinsic capacity to scavenge reactive oxygen species, thus mitigating oxidative stress. Additionally, their unique tetrahedral geometry facilitates endocytosis-mediated cellular uptake and confers them with excellent tissue permeability, enabling them to traverse the lung mucosal barrier. These properties collectively enhance cell-drug interactions. As a result, tFNAs show multidimensional therapeutic potential for the treatment of lung injuries and provide innovative strategies for managing complex pathological conditions. This review summarizes the recent advances in the application of tFNAs for lung injury repair, with a focus on their mechanisms of action, treatment strategies, and current challenges. The goal of this review is to promote breakthroughs in lung injury treatment.
Advancing Drug Discovery with AI: Machine and Deep Learning Strategies for Target Identification and Precision Nanomedicine.
Chakraborty A, Gholap AD, Khuspe PR … +5 more , Sundaram G, Webster TJ, Khalid M, Haris MS, Faiyazuddin M
Int J Nanomedicine · 2026 · PMID 42292041 · Full text
The integration of machine learning (ML) and deep learning (DL) into drug discovery and target identification has catalyzed a paradigm shift in pharmaceutical research, enhancing efficiency and translational potential fo...
The integration of machine learning (ML) and deep learning (DL) into drug discovery and target identification has catalyzed a paradigm shift in pharmaceutical research, enhancing efficiency and translational potential for nano-enabled therapeutics. ML models have demonstrated up to 85% accuracy in predicting drug-target interactions, whereas DL frameworks, such as convolutional neural networks (CNNs), graph neural networks (GNNs), and transformer architectures, can improve molecular property predictions by 40%. AI-driven drug discovery workflows have curtailed drug candidate attrition rates by up to 30% and accelerated discovery timelines by 20%-40%, accentuating their rising industrial and clinical impact. This critical review evaluates the transformative roles of ML and DL in the drug discovery pipeline, emphasizing their capacity to accelerate development timelines and advance precision nano medicine. We analyzed predictive modelling techniques, including quantitative structure-activity relationship (QSAR) and absorption, distribution, metabolism, and excretion (ADME) predictions, which streamline the identification of viable drug candidates, including nanocarrier-enabled drug systems. Virtual screening and bioactivity prediction further refine candidate prioritization, whereas target identification and validation leverage protein-ligand interaction modelling and biological pathway analysis to ensure therapeutic specificity. Additionally, we discuss the profound impact of DL on medical image analysis, genomic data interpretation, and protein structure prediction (PSP), which collectively advance structural bioinformatics and enable optimized targeted nano medicine. By synergizing ML and DL, multi-modal data fusion, explainable artificial intelligence (XAI), and nanotechnology-driven datasets, the drug discovery process is evolving into a more efficient, predictive, and patient-centric endeavor, paving the way for ground-breaking therapies and improved clinical outcomes.
ZnO Nanocrystals Inhibit Biofilms by Suppressing - and -Dependent EPS Biosynthesis.
Tian X, Zhou C, Bai Q … +8 more , Chen Y, Cai R, Lai J, Ye L, Feng W, Wang Y, Song Q, Liu T
Int J Nanomedicine · 2026 · PMID 42292040 · Full text
INTRODUCTION: Bacterial biofilms are a major cause of persistent and device-related infections due to their antibiotic resistance and ability to shelter bacteria. Zinc oxide nanocrystals (ZnO NCs), with their multiple an...
INTRODUCTION: Bacterial biofilms are a major cause of persistent and device-related infections due to their antibiotic resistance and ability to shelter bacteria. Zinc oxide nanocrystals (ZnO NCs), with their multiple antimicrobial mechanisms, have emerged as efficient antibacterial agents. METHODS: In this study, we synthesized rod-shaped ZnO NCs and evaluated their anti-biofilm efficacy against . Anti-biofilm activity was assessed at sub-minimum inhibitory concentration (MIC) and MIC levels. Transcriptomic analysis and qPCR were employed to examine gene expression changes in , with further mechanistic validation targeting specific metabolic pathways. RESULTS: At sub-MIC levels, ZnO NCs potently inhibited biofilm formation and eradicated pre-formed biofilms. These treatments also markedly suppressed the synthesis of key extracellular polymeric substances (EPS) components, while MIC-level treatments effectively degraded existing EPS in mature biofilms. Concurrently, ZnO NCs reduced overall EPS density, loosened biofilm architecture, and increased its structural heterogeneity. Furthermore, bacterial motility (swimming, twitching, and swarming) was strongly impaired across sub-MIC to MIC concentrations. Transcriptomic analysis revealed that ZnO NCs downregulated genes associated with biofilm formation, motility, and amino acid biosynthesis. qPCR indicated that the downregulation of and impaired the synthesis of key EPS components. CONCLUSION: Mechanistically, we validate that in , ZnO NCs suppress to disrupt glycogen-derived carbon precursors for polysaccharide synthesis, and downregulate to impair glutamate synthase activity, thereby limiting nitrogen assimilation and amino acid supply for proteinaceous EPS components. These findings elucidate a previously undefined mechanism wherein ZnO NCs dismantle biofilms by simultaneously targeting two pivotal metabolic nodes ( and ) that fuel EPS production. This work provides not only a deeper mechanistic insight into anti-biofilm action against but also supports the potential of ZnO NCs as multi-targeted anti-biofilm agents.
Chitosan-Based Wound Dressings: Property Modulation, Fabrication Strategies, and Emerging Applications in Tissue Regeneration.
Fan M, Zhang X, Lin L … +3 more , Tang R, Li H, Liu Y
Int J Nanomedicine · 2026 · PMID 42292039 · Full text
Chronic wounds are often difficult to heal because of multiple pathological barriers, including infection, vascular insufficiency, and immune imbalance, and therefore require highly effective dressings to promote repair....
Chronic wounds are often difficult to heal because of multiple pathological barriers, including infection, vascular insufficiency, and immune imbalance, and therefore require highly effective dressings to promote repair. Chitosan (CS), a cationic polysaccharide derived from the deacetylation of chitin, has attracted broad attention in wound management because of its favorable biocompatibility, biodegradability, chemical modifiability, and intrinsic hemostatic and antibacterial activities. The therapeutic value of CS-based dressings does not depend solely on CS itself, but rather on their ability to target the dominant pathological barriers of different wound types through structural modification and formulation design. This review links the key pathological features of various chronic wounds with the functional requirements of CS-based dressings, and systematically summarizes how modification strategies such as catechol grafting, quaternization, carboxymethylation, and dynamic covalent crosslinking regulate the properties of CS, as well as the major fabrication platforms and formulation types, including crosslinked hydrogels, freeze-dried sponges, electrospun nanofibers, phase-inversion membranes, and solvent-cast films. Their effects on porosity, mechanical strength, moisture retention, and permeability are also analyzed. Finally, the review discusses the challenges facing CS-based dressings in standardization, scalable manufacturing, clinical translation, and regulatory evaluation, and highlights the need for greater emphasis on multifunctional smart design and the improvement of evidence quality in future research.
Hydrogels in Neurological Disorders: Emerging Diagnostic and Therapeutic Applications.
Wang NN, Cao F, Xu D
Int J Nanomedicine · 2026 · PMID 42292038 · Full text
The clinical management of neurological disorders remains a major challenge worldwide, constrained by fundamental limitations in both diagnosis and therapy. Electroencephalography (EEG), the cornerstone of neurological a...
The clinical management of neurological disorders remains a major challenge worldwide, constrained by fundamental limitations in both diagnosis and therapy. Electroencephalography (EEG), the cornerstone of neurological assessment, is limited by low spatial resolution and inconsistent signal quality. Therapeutically, the blood-brain barrier (BBB) restricts drug delivery to the brain, resulting in subtherapeutic intracerebral concentrations. These convergent diagnostic and delivery bottlenecks underscore an urgent imperative for innovative materials and technologies. Hydrogels, characterized by biomimetic three-dimensional (3D) architectures, have emerged as a versatile material platform to bridge this gap. From a diagnostic perspective, hydrogels-based electrodes exhibit exceptional biocompatibility and low interfacial impedance, enabling high-fidelity EEG acquisition while minimizing insult to sensitive neural and skin tissues. From a therapeutic perspective, their 3D architecture provides versatile scaffolds for therapeutic agents, supporting high loading efficiency and programmable release profiles for neurological interventions. In this review, we first outline the physicochemical properties and fabrication techniques of hydrogels. We then discuss their applications, with particular emphasis on neural bio-electrodes, brain-computer interfaces (BCIs), drug delivery, and neuro-bioengineering. Finally, we examine the challenges impeding the clinical translation of hydrogels and outline prospective mitigation strategies. The integration of these functionalities is anticipated to advance closed-loop therapeutic systems for the precise management of complex neurological disorders.
Plant-Derived Exosome-Like Nanoparticles in Neurodegenerative Diseases: From Dual Bioactive-Delivery Roles to Translational Challenges.
Sun Y, Xu Z, Cui L … +3 more , Guo J, Zhang X, Xiao Y
Int J Nanomedicine · 2026 · PMID 42292037 · Full text
Neurodegenerative diseases, particularly Alzheimer's disease (AD) and related disorders, remain difficult to treat because of their multifactorial pathogenesis, limited disease-modifying therapies, and insufficient centr...
Neurodegenerative diseases, particularly Alzheimer's disease (AD) and related disorders, remain difficult to treat because of their multifactorial pathogenesis, limited disease-modifying therapies, and insufficient central nervous system exposure of many therapeutic agents. Plant-derived exosome-like nanoparticles (PELNs) are emerging as biogenic nanovesicles that combine intrinsic bioactivity with natural nanocarrier properties. Enriched with lipids, proteins, small RNAs, and phytochemicals, PELNs may exert neuroprotective effects while offering opportunities for gastrointestinal stability, systemic transport, and potential central nervous system delivery. This review critically summarizes the dual bioactive-delivery roles of PELNs in AD and related neurodegenerative disorders. We discuss their potential mechanisms in modulating neuroinflammation, glial cell-mediated immune responses, redox imbalance, mitochondrial dysfunction, pathological protein aggregation, neural repair, and gut-brain axis regulation. We further examine how administration routes, biodistribution patterns, cellular uptake, and blood-brain barrier (BBB) models influence the interpretation of evidence for central nervous system (CNS) targeting. In addition, recent advances in isolation, purification, characterization, cargo loading, and surface engineering strategies are reviewed in the context of improving stability, targeting capacity, and translational feasibility. Despite their promise, the clinical development of PELNs remains constrained by source-dependent heterogeneity, non-standardized isolation methods, insufficiently defined critical quality attributes, inconsistent dosing metrics, limited pharmacokinetic and biodistribution data, and unresolved long-term biosafety concerns. Establishing rigorous Chemistry, Manufacturing, and Controls (CMC) frameworks, reproducible quality-control assays, and evidence-based translational pathways will be essential for advancing PELNs from experimental bioactive vesicles to clinically relevant neurotherapeutic platforms.
Nanotechnology-Driven Drug-Delivery Systems: Mechanistic Insights for Pediatric Autism Treatment in 2026.
Atashgahi M, Madani F, Webster TJ
Int J Nanomedicine · 2026 · PMID 42292036 · Full text
Autism spectrum disorder (ASD) is a diverse neurodevelopmental disorder that commences in early childhood, characterized by enduring social-communication challenges, limited interests, and behavioral rigidity. The manage...
Autism spectrum disorder (ASD) is a diverse neurodevelopmental disorder that commences in early childhood, characterized by enduring social-communication challenges, limited interests, and behavioral rigidity. The management of ASD continues to pose significant difficulties in pediatric practice. Converging evidence implicates abnormalities in synaptic scaffolding and transmission, excitation-inhibition imbalance, mTOR/PI3K-AKT signaling, neuroinflammation, gut-brain axis, and metabolic disturbances, highlighting multiple cellular and molecular targets for potential therapeutic development. Nonetheless, contemporary care is primarily characterized by non-pharmacological interventions and symptomatic pharmacological treatments, with a scarcity of strategies that alter fundamental mechanisms. The blood-brain barrier (BBB) is a significant hurdle to overcome - its structure, transport routes, and context-specific dysfunction in ASD both limit and create opportunities for central nervous system (CNS) drug delivery at the same time. In this context, nanomedicine presents novel opportunities and nanoparticles are currently emerging for various neurological applications in preclinical and clinical studies. They can be designed for targeted drug delivery to the brain, for the development of sophisticated ASD models and for diagnostic and theranostic purposes. This review incorporates the clinical manifestations, mechanistic pathways, BBB biology, and nanoparticle-based methodologies to provide a developmentally informed framework for nano-enabled interventions in ASD.
ROS-Triggered Self-Aggregation of a β-Elemene Olefin-Rich Nanoemulsion for Mitochondrial-Targeted Metabolic Reprogramming and Colitis Inflammation Alleviation.
Luo Z, Jia L, Tang Y … +6 more , Huang Y, Ma Z, Li Y, Zhang X, Zhang P, Xie T
Int J Nanomedicine · 2026 · PMID 42292035 · Full text
PURPOSE: Inflammatory bowel disease (IBD) is a chronic condition driven by pro-inflammatory macrophages. Although natural compounds with carbon-carbon double bonds (C=C bonds), such as β‑elemene, exhibit anti-inflammator...
PURPOSE: Inflammatory bowel disease (IBD) is a chronic condition driven by pro-inflammatory macrophages. Although natural compounds with carbon-carbon double bonds (C=C bonds), such as β‑elemene, exhibit anti-inflammatory properties, their precise subcellular targets and mechanisms remain elusive. This study aimed to develop a targeted nanomedicine to elucidate the anti-inflammatory mechanism of β‑elemene and establish a novel therapeutic strategy for colitis. PATIENTS AND METHODS: We engineered a reactive oxygen species (ROS)-responsive β‑elemene nanoemulsion (ELE-NE) for targeted drug delivery. Its therapeutic efficacy and mechanism were evaluated in a murine model of dextran sulfate sodium (DSS)-induced colitis. A mitochondria-targeted, ROS-activatable near-infrared probe was also developed for in vivo imaging tracking of inflammatory foci and assessment of therapeutic efficacy. RESULTS: In DSS-induced colitis mice, ELE-NE preferentially accumulated in inflamed colon tissue and effectively alleviated disease pathology. Mechanistically, upon reaching inflammatory macrophages, ELE-NE utilized the pathological ROS surge to undergo spatially confined aggregation at mitochondrial sites. This nano-aggregation directly disrupted the electron transport chain (ETC), potently suppressing oxidative phosphorylation and reprogramming cellular energy metabolism. Consequently, this mitochondria-focused metabolic intervention attenuated M1 macrophage polarization, reduced pro-inflammatory cytokine secretion. CONCLUSION: This is the first report demonstrating that β‑elemene acts via ROS‑triggered mitochondrial aggregation and metabolic reprogramming. We deciphered the mechanism of β-elemene, revealing that its olefinic (C=C) functional group enables bioresponsive mitochondrial aggregation and metabolic reprogramming, thereby proposing the concept of "olefinic drugs" as a distinct therapeutic class. Furthermore, we established a novel theranostic paradigm for treating inflammatory diseases using olefinic nanomedicines, enabled by a companion imaging tool for non‑invasive detection of inflammatory foci and dynamic monitoring of the treatment process.
Melittin-Loaded FeO-Au Nanocomposite Hydrogel for Multifunctional Treatment of Atopic Dermatitis.
Xu WC, Duan XQ, Zhong L … +12 more , Li YC, Ran L, Xu HH, Wu Q, Huang K, Miao NN, Jiang T, Chen QH, Zhang Y, Zhang HZ, Wang RP, Gong M
Int J Nanomedicine · 2026 · PMID 42292034 · Full text
BACKGROUND: Atopic dermatitis (AD) severely impairs the lives of patients and existing therapies are limited by side effects or insufficient efficacy. In this study, we developed a multifunctional nanocomposite hydrogel...
BACKGROUND: Atopic dermatitis (AD) severely impairs the lives of patients and existing therapies are limited by side effects or insufficient efficacy. In this study, we developed a multifunctional nanocomposite hydrogel that integrates immunoregulation, antioxidant, antibacterial, and skin repair for the integrative treatment of AD. METHODS: FeO-Au (FA) nanoparticles (NPs) were synthesized, melittin (MLT) was anchored onto FA NPs, and MLT-FeO-Au (MFA) was loaded into Pluronic F-127 (PF127), to prepare the MFA@PF127 hydrogel. After a comprehensive evaluation of the physicochemical properties, MFA@PF127 was incubated with HaCaT cells and administered to AD lesions to demonstrate its therapeutic efficiency for AD in vitro and in vivo. RESULTS: The FeO‑Au (FA) NPs with a heterodimer morphology and uniform size were successfully prepared, and the MLT was then loaded onto FA NPs with a high loading efficiency of 64.5%. By loading MLT-FA (MFA) NPs into PF127, the MFA@PF127 nanocomposite hydrogel with thermosensitivity, a porous structure, and good biocompatibility was successfully constructed. After incubation with MFA@PF127 and irradiated with near-infrared (NIR) laser, HaCaT cells showed significantly lower thymic stromal lymphopoietin (TSLP) expression and reactive oxygen species (ROS) levels than the control. The growth of and biofilm formation were suppressed by MFA@PF127 under NIR irradiation. When administered to AD lesions, MFA@PF127+NIR significantly alleviated the dermatitis severity score; downregulated TSLP, IL‑4, and IL‑13 expression, suppressed colonization; reduced ROS levels; and alleviated epidermal thickening and mast cell infiltration. CONCLUSION: MFA@PF127 exhibited multifunctionality of immunoregulation, and antioxidant and antibacterial activities, which significantly alleviated AD symptoms in a mouse model and provided a potential strategy for AD treatment after further preclinical validation.
Nature-Inspired Alternatives to PEG for Next-Generation Long-Circulating Nanocarriers.
Jan N, Rejili M
Int J Nanomedicine · 2026 · PMID 42292033 · Full text
Polyethylene glycol (PEG) has long been considered as the gold standard for imparting stealth properties to nanocarriers. However, the recent emergence of anti-PEG antibodies has spurred innovation toward nature-inspired...
Polyethylene glycol (PEG) has long been considered as the gold standard for imparting stealth properties to nanocarriers. However, the recent emergence of anti-PEG antibodies has spurred innovation toward nature-inspired alternatives. By mimicking the structural and functional architectures of biological systems such as cell membranes and protein corona, nanocarriers can be engineered to achieve prolonged circulation, superior biocompatibility, and active targeting capabilities. This perspective presents nature-inspired alternatives to PEG, including cell membranes and the protein corona, for extending the circulation time of nanocarriers. It also highlights current challenges associated with these nature-inspired alternatives and outlines future research directions to overcome these hurdles in designing next-generation long-circulating nanocarriers.
Engineered Nanomaterials for Drug Delivery in Temporomandibular Joint Osteoarthritis: Translational Insights and Current Advances.
Sun S, Jiang Y, Zhang J … +2 more , Zhang S, Xu Y
Int J Nanomedicine · 2026 · PMID 42281924 · Full text
Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disorder involving cartilage degeneration, synovial inflammation, and abnormal bone remodeling. Current clinical treatments are limited by low delivery ef...
Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disorder involving cartilage degeneration, synovial inflammation, and abnormal bone remodeling. Current clinical treatments are limited by low delivery efficiency and short intra-articular drug retention. This review summarizes recent advances in nanotechnology-based drug delivery systems for TMJ OA therapy. Various nanocarriers, including liposomes, polymer nanoparticles, nanomicelles, metal-organic frameworks, and hydrogels, have been investigated for their ability to improve joint targeting, extend intra-articular residence time, and enable sustained or stimuli-responsive drug release. In addition, emerging nanomaterials, such as nanozymes, inorganic nanomaterials, and carbon-based materials, show potential in modulating the inflammatory microenvironment and supporting cartilage repair. However, most current evidence is derived from non-TMJ OA models or related nanoplatform studies, and direct TMJ-specific validation remains limited, which constrains translational interpretation. Despite these advances, several challenges remain, including limited penetration across physiological barriers, insufficient durability of therapeutic effects, and unresolved safety issues in clinical translation. Future studies should place greater emphasis on TMJ-specific validation, the development of intelligent responsive delivery systems, and the establishment of standardized evaluation approaches. The integration of patient-specific factors may further support precision treatment and facilitate the clinical translation of nanotherapeutic strategies for TMJ OA.
Glucose-Responsive Dual-Enzyme Mimetic Nanoreactor Remodels Diabetic Periodontitis Microenvironment for Augmented Alveolar Bone Regeneration.
Wang D, Chen J, Wang J … +3 more , Chen H, Li W, Shen S
Int J Nanomedicine · 2026 · PMID 42281923 · Full text
BACKGROUND: Periodontitis in the context of diabetes severely disrupts bone metabolic homeostasis, leading to irreversible alveolar bone loss. The resulting alveolar bone defects face significant challenges in healing du...
BACKGROUND: Periodontitis in the context of diabetes severely disrupts bone metabolic homeostasis, leading to irreversible alveolar bone loss. The resulting alveolar bone defects face significant challenges in healing due to a pathological microenvironment characterized by the interplay of hyperglycemia, oxidative stress, infection, and inflammation. Existing therapeutic strategies often lack the capability to synchronously and intelligently regulate this complex milieu, resulting in delayed and inefficient bone repair. METHODS: A composite material, termed MTS@QP-G@CO, was developed. Its core consists of manganese dioxide (MnO) nanoflowers loaded with a tannic acid (TA) -strontium metal (Sr)-phenolic network. These were conjugated with glucose oxidase via phenylboronic acid bonding and encapsulated within a pH-responsive Schiff base hydrogel. The structural characterization of the material, the performance of the cascade reaction, as well as its antioxidant and antibacterial properties have all been fully verified. A series of in vitro and in vivo experiments were conducted to evaluate the system's efficacy in modulating the local metabolic and oxidative status, inducing macrophage polarization, promoting osteogenic differentiation, and restoring bone regeneration in diabetic alveolar bone defect models. RESULTS: The MTS@QP-G@CO designed sequential action at the defect site involves triggering a "glucose starvation" effect via glucose oxidase, followed by hydrogen peroxide decomposition and oxygen generation catalyzed by the MnO nanozyme. This achieves synchronized glucose reduction, hypoxia alleviation, reactive oxygen species (ROS) scavenging, and antibacterial activity. Subsequently, TA and Sr are programmable released. And the system effectively remodeled the local pathological microenvironment in diabetic bone defects. It successfully achieved synchronized precise glucose reduction, hypoxia alleviation, ROS scavenging, and bacterial inhibition. This was followed by the cooperative release of therapeutic ions, which modulated the immune microenvironment by suppressing inflammation and inducing macrophage polarization toward the pro-healing M2 phenotype. Consequently, the system accelerated early osteogenic differentiation and bone matrix maturation, transforming the disordered repair process into a coordinated and efficient regeneration, leading to high-quality bone repair. CONCLUSION: The MTS@QP-G@CO system effectively reverses the pathological microenvironment, coordinates immune modulation and osteogenesis, and transforms delayed healing into efficient, high-quality bone regeneration, offering a promising therapeutic approach for diabetes-related bone defects.
Cyclodextrin-Based Nanocarriers for 5-Fluorouracil: Cholesteryl Modification Enhances Antitumor Activity Against Colorectal Cancer Cells.
Skonieczna B, Maliszewski B, Wasiluk N … +4 more , Car H, Wilczewska AZ, Misiak P, Niemirowicz-Laskowska K
Int J Nanomedicine · 2026 · PMID 42273177 · Full text
BACKGROUND: The objective of this study is to evaluate the biological activity of cholesterol-modified cyclodextrin (CD21chol) complexes with 5-fluorouracil (5-FU) prepared at different molar ratios (1:1, 1:2, and 1:3) a...
BACKGROUND: The objective of this study is to evaluate the biological activity of cholesterol-modified cyclodextrin (CD21chol) complexes with 5-fluorouracil (5-FU) prepared at different molar ratios (1:1, 1:2, and 1:3) and to identify the most potent anticancer formulation. METHODS: The inclusion complexes of CD21chol:5-FU were prepared at different molar ratios (1:1, 1:2, and 1:3) and initially characterized based on their physicochemical properties, such as increased negative surface charge and particle size. Subsequently, the biological activity was investigated in the human colorectal cancer cell line DLD-1 by analyzing cell viability, metabolic activity, membrane integrity, and apoptosis (activation of caspases 3/7, 8, and 9). Cytotoxicity was also measured in non-tumorigenic fibroblasts and cardiomyocytes. RESULTS: The complexation with 5-FU resulted in a shift toward more negative zeta potential values, with the 1:3 CD21chol:5-FU system showing the greatest change and improved physicochemical stability. Particle size analysis revealed a reduction in hydrodynamic diameter at lower drug ratios (1:1 and 1:2), followed by an increase at the 1:3 ratio. Biologically, the 1:3 complex exerted the strongest cytotoxic effect against DLD-1 cells, reducing metabolic activity and cell viability by over 60%, increasing LDH release, and significantly activating caspases 3/7, 8, and 9, indicating engagement of both intrinsic and extrinsic apoptotic pathways. In contrast, only moderate toxicity was observed in CCD-1079SK fibroblasts and H9c2(2-1) cardiomyocytes. CONCLUSION: The results indicate that CD21chol-based delivery systems enhance the anticancer activity of 5-FU. The 1:3 complex appears to be the most promising candidate for further development in colorectal cancer therapy.
Early Screening for Cervical Squamous Cell Carcinoma and Precancerous Lesions Based on Surface-Enhanced Raman Spectroscopy Microarray Chips.
Xia J, Sun J, Lu D
Int J Nanomedicine · 2026 · PMID 42273176 · Full text
BACKGROUND: MicroRNAs (miRNAs) play a significant role in the development, progression, invasion and metastasis of tumours. Their serum concentrations are closely associated with the progression of tumour diseases and ho...
BACKGROUND: MicroRNAs (miRNAs) play a significant role in the development, progression, invasion and metastasis of tumours. Their serum concentrations are closely associated with the progression of tumour diseases and hold promise for cancer diagnosis. This study developed a microarray chip based on surface-enhanced Raman scattering (SERS) technology for the highly sensitive detection of cervical cancer biomarkers (miRNA103a and miRNA221). The combination of SERS technology with the microarray chip enables the simultaneous and repeatable detection of multiple samples. METHODS: An array of gold-silver nanoboxes (Au-AgNBs) was constructed via self-assembly at the oil-water interface and anchored within the wells of the microarray chip. Capture DNA (DNAmiRNA103a-Cy3 and DNAmiRNA221-Cy5) was immobilised on the surface of the Au-AgNBs array via gold-sulphur bonds to serve as the capture matrix, thereby constructing the microarray chip. When signal molecules approach the substrate, the SERS signal intensity is enhanced. When target molecules (miRNA103a and miRNA221) are present in the detection environment, they bind to the corresponding capture DNA via complementary base pairing, forming double-stranded nucleic acids. Upon the addition of a double-stranded nucleic acid-specific nuclease (DSN nuclease), the double strand is specifically cleaved, releasing the signal molecules and resulting in a decrease in the SERS signal intensity in the detection environment. The characteristics of the microarray chip, including reproducibility and sensitivity, were characterised. Microarray chips and qRT-PCR were used to detect miRNA103a and miRNA221 in the serum of 30 healthy individuals (control group), 30 patients with low-grade cervical intraepithelial neoplasia (LSIL), 30 patients with high-grade cervical intraepithelial neoplasia (HSIL), and 30 patients with cervical cancer (stage 1A). RESULTS: The prepared microarray chip demonstrated good reproducibility and sensitivity. Under optimal testing conditions, the lower limits of detection for miRNA-103a and miRNA-221 on the microarray chip were 1.0934 × 10 M/L and 7.5667 × 10 M/L, respectively. Serum samples from healthy subjects, patients with LSIL, HSIL and cervical cancer (stage 1A) were analysed, and the results were compared with those obtained using the qRT-PCR method. The relative error between the two methods was less than 10%, and the results were statistically significant (P < 0.05). CONCLUSION: Microarray chips provide a reliable new method for the early screening of cervical cancer. This simple and efficient microarray chip preparation method demonstrates excellent potential for application in experiments involving multiple samples and replicates. Microarray chips exhibit excellent ability to distinguish between disease states, capable of differentiating between healthy individuals, patients with LSIL, HSIL and cervical cancer.
Mitochondria-Targeted MPDA Nanosystem Co-Delivering Evodiamine and IR820 for Chemo-Photothermal Therapy of Hepatocellular Carcinoma.
Kong S, Lin H, Liu Y … +3 more , Tang R, Li H, Lin L
Int J Nanomedicine · 2026 · PMID 42273175 · Full text
INTRODUCTION: Hepatocellular carcinoma (HCC) is a highly malignant tumor characterized by considerable heterogeneity, aggressive invasiveness, and a high recurrence rate. Monotherapy often yields limited clinical efficac...
INTRODUCTION: Hepatocellular carcinoma (HCC) is a highly malignant tumor characterized by considerable heterogeneity, aggressive invasiveness, and a high recurrence rate. Monotherapy often yields limited clinical efficacy, and evodiamine (EVO), a natural alkaloid with promising antitumor activity, is hindered by low bioavailability and potential systemic toxicity. METHODS: A mesoporous polydopamine (MPDA)-based theranostic nanosystem was constructed for the co-delivery of EVO and the photothermal agent IR820. To enhance tumor specificity and minimize off-target toxicity, the platform was functionalized with cyclic RGD (cRGD) peptides for active tumor homing and triphenylphosphonium (TPP) for mitochondrial localization. The resulting IR820/EVO@MPDA-TPP/cRGD nanoparticles were characterized for drug loading, photothermal conversion stability, and fluorescence properties, and evaluated for antitumor efficacy and mechanistic actions in vivo. RESULTS: The nanosystem demonstrated high drug loading efficiencies, excellent photothermal conversion stability, and robust near-infrared fluorescence emission suitable for real-time diagnostic tracing. Upon NIR laser irradiation, IR820/EVO@MPDA-TPP/cRGD exhibited potent synergistic anticancer activity and significantly inhibited tumor growth in vivo. Mechanistically, the combined photothermal and chemotherapeutic effects triggered severe mitochondrial dysfunction, leading to the collapse of mitochondrial membrane potential and subsequent release of pro-apoptotic factors. DISCUSSION: The dual-targeting strategy effectively shifted cellular homeostasis toward programmed cell death while simultaneously engaging quality control pathways, underscoring a mitochondria-centered mechanism linking photothermal effect and chemotherapy. CONCLUSION: IR820/EVO@MPDA-TPP/cRGD represents a dual-targeting theranostic nanoplatform that integrates imaging and chemo-photothermal combination therapy. This strategy offers a promising and clinically relevant approach for advanced HCC.
PLGA-PEG Nano-Adjuvant-Delivered ClfA Vaccine Elicits IL-17A-Mediated Neutrophil Activation to Confer Complete Protection Against Methicillin-Resistant .
Shi Z, Wan Z, Tan G … +12 more , Xi J, Cui M, Hou Y, Ma Z, Sun N, Zhu Y, Li M, Wang D, He X, Yang Q, Song C, Fan L
Int J Nanomedicine · 2026 · PMID 42267312 · Full text
PURPOSE: Methicillin-resistant (MRSA) is a major cause of severe, life-threatening infections worldwide, highlighting an urgent and unmet need for effective vaccines. Current () vaccine candidates predominantly employ...
PURPOSE: Methicillin-resistant (MRSA) is a major cause of severe, life-threatening infections worldwide, highlighting an urgent and unmet need for effective vaccines. Current () vaccine candidates predominantly employ aluminum-based adjuvants, which potently induce Th2-biased humoral immunity but fail to adequately elicit protective Th1/Th17 cellular responses. Given that Th1 and Th17 responses are critical for clearance of infection, developing an adjuvant platform capable of redirecting immunity toward these pathways is urgently needed. To address this limitation, we aimed to develop a novel nano-vaccine and systematically evaluate its immunogenicity and protective efficacy. METHODS: We constructed a nano-vaccine using PLGA-PEG-COOH nanoparticles (25%NPs) as the adjuvant and recombinant clumping factor A (rClfA) as the antigen. The immunogenicity of the 25%NPs-rClfA vaccine was compared with that of an aluminum-adjuvanted formulation. Specific antibody levels, neutralizing activity, and cytokine production (IFN-γ and IL-17A) were measured. Protective efficacy was assessed by challenging immunized subjects with a lethal dose of strain ATCC25923. Mechanistic studies included evaluation of neutrophil phagocytosis and reactive oxygen species (ROS) release. The necessity of the Th17 pathway was confirmed via IL-17A blockade experiments. RESULTS: Compared to the aluminum-adjuvanted vaccine, the 25%NPs-rClfA nano-vaccine elicited lower specific antibody titers but generated antibodies with superior neutralizing activity. It significantly enhanced the secretion of IFN-γ and IL-17A, with IL-17A sustaining elevated levels over an extended period. Crucially, the nano-vaccine conferred 100% protection against death following lethal challenge. Mechanistically, it enhanced neutrophil phagocytosis and ROS production-key processes for bacterial clearance. Blockade of the Th17 pathway abrogated vaccine protection, demonstrating that IL-17A is essential for its efficacy. CONCLUSION: This study demonstrates that the PLGA-PEG nanoparticle-based rClfA nano-vaccine can effectively redirect immune responses toward protective Th1/Th17 immunity and robustly protect against lethal infection, largely through an IL-17A-dependent mechanism. These findings provide important experimental and theoretical support for the translational development of vaccines.
Diselenide-Bridged Iron-Porphyrin MOF for MRI-Guided Radiotherapy via Triple-Pathway Ferroptosis.
Huang W, Zheng G, Mo B … +6 more , Jing G, Gao M, Zhao J, Liu H, Luo S, Yu S
Int J Nanomedicine · 2026 · PMID 42267311 · Full text
INTRODUCTION: Radiation resistance poses a significant challenge in clinical cancer therapy. Ferroptosis, an iron-dependent form of cell death, plays an important role in the efficacy of radiotherapy. However, cancer cel...
INTRODUCTION: Radiation resistance poses a significant challenge in clinical cancer therapy. Ferroptosis, an iron-dependent form of cell death, plays an important role in the efficacy of radiotherapy. However, cancer cells often activate defense systems to survive this process. Moreover, interventions targeting only a single defense pathway often yield limited effects. METHODS: To overcome radioresistance, we have developed a reactive oxygen species (ROS)-responsive nanosystem named PRBP. This system employs a siderophore-based framework PCN(Fe) as the core, loaded with two specific drugs: RAS-selective lethal compound 3 (RSL3) to block the glutathione peroxidase 4 (GPX4) pathway, and brequinar (BQR) to inhibit the dihydroorotate dehydrogenase (DHODH) pathway. The surface is coated with a diselenide bond-linked polyethylene glycol (PEG-Se-Se-PEG) layer that dissociates in a ROS-rich environment. Upon X-ray irradiation, the system rapidly degrades and releases the drugs, while iron ions trigger the Fenton reaction. RSL3 and BQR synergistically suppress the ferroptosis defense system, inducing a potent "ferroptosis storm." Through in vitro and in vivo experiments, we systematically evaluated the physical properties, magnetic resonance imaging (MRI) capability, and therapeutic efficacy of this platform. RESULTS: PRBP exhibits a uniform morphology and undergoes responsive degradation under X-ray irradiation, releasing Fe to catalyze the Fenton reaction, leading to DNA damage and glutathione (GSH) depletion. Meanwhile, RSL3 and BQR inhibit the GPX4 and DHODH pathways, respectively, blocking multiple ferroptosis defense targets and thereby inducing robust ferroptosis. PRBP demonstrates favorable T1-weighted magnetic resonance imaging performance, significantly inhibits tumor cell proliferation in vitro, effectively suppresses 4T1 tumor growth in vivo, and exhibits good biosafety. CONCLUSION: PRBP induces ferroptosis through multiple targets, providing a potent strategy to overcome radiotherapy resistance.
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