International Journal Of Nanomedicine[JOURNAL]
Sun
200 papers
Prenatal Delivery of HIF-1α siRNA Using Transferrin-Modified Lipid Nanoparticles Alleviates Hypoxia-Induced Neurodevelopmental Abnormalities via PTEN/PI3K/AKT Signaling.
Du F, Bai Y, Bai K … +4 more , Yang T, Chen J, Li T, Dai Y
Int J Nanomedicine · 2026 · PMID 42152976 · Full text
PURPOSE: Prenatal hypoxia is a major environmental risk factor for neurodevelopmental disorders, yet effective prenatal therapeutic strategies remain lacking. This study aimed to develop a transferrin-modified lipid nano...
PURPOSE: Prenatal hypoxia is a major environmental risk factor for neurodevelopmental disorders, yet effective prenatal therapeutic strategies remain lacking. This study aimed to develop a transferrin-modified lipid nanoparticle platform for targeted delivery of HIF-1α siRNA to the fetal brain and to evaluate its therapeutic efficacy and molecular mechanisms. METHODS: Transferrin-modified lipid nanoparticles encapsulating HIF-1α siRNA were intravenously administered to pregnant rats prior to hypoxic exposure. Biodistribution, gene silencing efficiency, molecular signaling alterations, neuronal structural changes, and behavioral outcomes in offspring were systematically assessed. RESULTS: In this study, we developed a transferrin-modified lipid nanoparticle system for non-invasive, transplacental delivery of HIF-1α small interfering RNA to the fetal brain, achieving a siRNA encapsulation efficiency of 84.18% and a loading capacity of 2.5%. Systemic administration to pregnant rats prior to hypoxic exposure resulted in preferential accumulation of nanoparticles in fetal brain tissue and effective suppression of HIF-1α expression in the fetal hippocampus without overt effects on offspring survival, as evidenced by comparable offspring survival rates across all groups (p > 0.05). Prenatal hypoxia induced sustained elevation of HIF-1α protein (p < 0.001), impaired phosphatase and tensin homolog (PTEN) activity through increased phosphorylation (p < 0.01), aberrant activation of the PI3K/AKT signaling pathway (p < 0.05), and deficits in hippocampal neuronal structural plasticity, including reduced dendritic spine density (p < 0.0001) and dendritic complexity (p < 0.0001), accompanied by autism-like behaviors in offspring, including impaired social preference (p < 0.01), prolonged self-grooming (p < 0.0001), and increased marble-burying (p < 0.001). Prenatal HIF-1α silencing restored PTEN functional status, normalized PI3K/AKT signaling, improved dendritic architecture to levels comparable to controls (p > 0.05 vs control), and significantly ameliorated behavioral abnormalities (social preference and stereotyped behaviors, p < 0.0001). Mechanistic analyses revealed that although HIF-1α binds to the PTEN promoter (ChIP-qPCR, p < 0.01), prenatal hypoxia did not alter PTEN transcript or total protein levels (p > 0.05), indicating that HIF-1α primarily regulates PTEN function at the post-transcriptional level in vivo. CONCLUSION: These findings identify a HIF-1α/PTEN/PI3K/AKT signaling axis as a key molecular pathway underlying hypoxia-associated neurodevelopmental impairment and demonstrate the feasibility of targeted prenatal gene modulation using transferrin-modified lipid nanoparticles. This work provides a nanomedicine-based framework linking environmental risk factors to early-life preventive strategies for neurodevelopmental disorders.
Therapeutic Metal Ions: Engineering Biomaterials for Multimodal Disease Treatment.
Liu Y, Wu X, Su X … +1 more , Li X
Int J Nanomedicine · 2026 · PMID 42152975 · Full text
Metal ions possess unique catalytic, immunomodulatory, and antimicrobial properties, demonstrating multimodal therapeutic potential in chemodynamic therapy, tumor immunotherapy, tissue regeneration, and anti-infective ap...
Metal ions possess unique catalytic, immunomodulatory, and antimicrobial properties, demonstrating multimodal therapeutic potential in chemodynamic therapy, tumor immunotherapy, tissue regeneration, and anti-infective applications. This review systematically outlines metal-based biomaterials, including metal-organic frameworks, nanoparticles, mixed matrix membranes, and protein-inspired metal polymers, as well as design strategies such as multi-metal synergy, dynamic responsiveness, biomimetic structures, and three-dimensional printing. Drawing on the principles of coordination chemistry, electron transfer, and signaling pathway interference, we elucidate the core mechanisms by which metal ions regulate cell death, immune responses, and tissue regeneration. Nevertheless, approximately 85% of current research remains at or below the cellular level, with in vivo studies accounting for less than 85%, and human clinical studies are completely lacking. Most metal ions have a narrow therapeutic window; non-specific release may induce oxidative stress and organ toxicity, and the long-term in vivo behavior of engineered carriers remains poorly understood. Key translational challenges include the absence of standardized guidelines for evaluating release kinetics and toxicology, difficulties in scalable manufacturing and batch-to-batch consistency, and unpredictable interactions with the host's endogenous metal pool and immune system. In summary, metal-based biomaterials exhibit broad application value and unique therapeutic potential in the fields of antitumor therapy, anti-infection, tissue repair, and theranostics. Although current readiness for clinical translation remains at an early stage, the translational potential of these materials warrants further investigation. Future efforts should focus on systematic in vivo validation and optimization of material design to facilitate progression toward clinical application.
Drug Delivery Engineering Strategies Targeting CD4+/CD8+ T Cell Exhaustion to Improve the Tumor Immunosuppressive Microenvironment.
Yue J, Chen M, Xiong Z … +3 more , Qiu J, Liu Y, Chen L
Int J Nanomedicine · 2026 · PMID 42146300 · Full text
CD4⁺/CD8⁺ T cell exhaustion, characterized by impaired effector function, sustained expression of inhibitory receptors, and diminished proliferative capacity, is a core driver in the formation of the tumor immunosuppress...
CD4⁺/CD8⁺ T cell exhaustion, characterized by impaired effector function, sustained expression of inhibitory receptors, and diminished proliferative capacity, is a core driver in the formation of the tumor immunosuppressive microenvironment (TME) and a major obstacle to antitumor immunotherapy. Nanomaterial-based drug delivery systems (NDDSs) have emerged as potential tools for targeting exhausted T cells (Tex), leveraging their unique advantages in precise targeting, controlled release, enhanced bioavailability, and reduced off-target toxicity. This article reviews the latest advances in NDDS-mediated delivery strategies targeting CD4⁺/CD8⁺ Tex cells, encompassing the delivery of immune checkpoint inhibitors, cytokines, small molecule modulators, and nucleic acid drugs. These strategies aim to reverse Tex cell dysfunction by modulating key molecular pathways involved in T cell exhaustion (like, PD-1/PD-L1, CTLA-4, NF-κB, and STAT signaling pathways), thereby enhancing T cell-mediated antitumor immune responses and remodeling the tumor immunosuppressive microenvironment. Finally, the challenges and prospects of utilizing NDDSs to target T cell exhaustion for tumor immunotherapy are briefly discussed, providing a reference for the development of novel antitumor therapeutic strategies.
Impacts of a Nano-Laponite Ceramic on Surface Performance, Apatite Mineralization, Cell Response, and Osseointegration of a Polyimide-Based Biocomposite [Retraction].
Int J Nanomedicine · 2026 · PMID 42146299 · Full text
[This retracts the article DOI: 10.2147/IJN.S273240.].
[This retracts the article DOI: 10.2147/IJN.S273240.].
Albumin Pre-Coating Enhances Intracellular siRNA Delivery of Multifunctional Amphiphile/siRNA Nanoparticles [Retraction].
Int J Nanomedicine · 2026 · PMID 42146298 · Full text
[This retracts the article DOI: 10.2147/IJN.S34288.].
[This retracts the article DOI: 10.2147/IJN.S34288.].
Precision Engineering of Extracellular Vesicles as Programmable Carriers for mRNA Therapeutics.
Yoon H, Lee G, Jo J … +7 more , Koo J, Kim EH, Choi HJ, Jung S, Shin Y, Oh KT, Lim C
Int J Nanomedicine · 2026 · PMID 42146297 · Full text
Messenger RNA (mRNA) therapeutics have rapidly evolved into a transformative modality for treating infectious diseases, cancer, and genetic disorders; however, the clinical translation of these therapeutics remains limit...
Messenger RNA (mRNA) therapeutics have rapidly evolved into a transformative modality for treating infectious diseases, cancer, and genetic disorders; however, the clinical translation of these therapeutics remains limited by the need for safe, efficient, and tissue-specific delivery vehicles. Subsequently, extracellular vesicles (EVs) have emerged as a promising next-generation platform due to the associated endogenous biogenesis, intrinsic biocompatibility, low immunogenicity, and natural ability to traverse biological barriers. Thus, this review provides a comprehensive evaluation of the major engineering strategies enabling EV-based mRNA delivery, including exogenous loading methods, endogenous genetic engineering, physical microenvironment-driven enhancement, and hybrid EV-synthetic nanoparticle systems. Moreover, this review summarizes advances in electroporation, lipid-mediated fusion, and chemical/physical loading techniques; programmable endogenous loading platforms leveraging EV-sorting proteins and RNA-binding domains; cargo release mechanisms employing self-cleaving, protease-sensitivity, and optogenetic modules; device- and substrate-based approaches that modulate EV biogenesis and cargo composition. We further highlight emerging hybrid EV systems-particularly fusogenic cubosome-EV constructs-that achieve near-quantitative mRNA encapsulation and improved biodistribution, including enhanced penetration across the blood-brain barrier. Finally, we discuss technological bottlenecks and translational considerations, including scalability, batch variability, long-term mRNA stability, and regulatory challenges associated with biologically derived carriers. Collectively, this review outlines the current landscape and future directions for precision engineering of EVs as programmable, clinically viable carriers for mRNA therapeutics.
Role of Extracellular Vesicles in Skin Barrier Repair: Applications in Atopic Dermatitis and Chronic Wounds.
Khoo L, Chin YZ, Law JX
Int J Nanomedicine · 2026 · PMID 42137193 · Full text
Extracellular vesicles (EVs) have emerged as a promising cell-free therapeutic strategy for skin barrier repair due to their ability to mediate intercellular communication through the delivery of bioactive cargo includin...
Extracellular vesicles (EVs) have emerged as a promising cell-free therapeutic strategy for skin barrier repair due to their ability to mediate intercellular communication through the delivery of bioactive cargo including proteins, lipids, and nucleic acids. This review synthesises current evidence on the role of EVs in restoring skin barrier integrity, with a particular focus on atopic dermatitis (AD) and chronic wounds. EVs derived from mesenchymal stromal cells, epidermal cells, and commensal microbiota exhibit distinct but overlapping therapeutic properties, including immunomodulation, promotion of keratinocyte proliferation and differentiation, and stimulation of dermal remodelling and angiogenesis. These effects are mediated through key signalling pathways such as AKT, ERK, NF-κB, Wnt/β-catenin, and HIF-1α/VEGF, as well as through regulatory microRNAs that fine tune cellular responses. Importantly, the relative contribution of these mechanisms is context dependent, with immune modulation predominating in AD and angiogenesis and tissue regeneration playing a central role in chronic wound healing. Despite strong preclinical evidence demonstrating efficacy, translation into clinical application remains limited by challenges in delivery, standardisation, and scalability. This review highlights the therapeutic potential of EV while emphasising the need for improved delivery strategies and rigorously designed clinical studies to fully realise their clinical utility in skin barrier repair.
Source-Specific Extracellular Vesicle Functions and Engineering Strategies for Chronic Pain Management: A Comprehensive Review.
Yao C, Yu J, Xie D … +6 more , Zhang S, Tao J, Kong L, Fang L, Zhu Q, Fang M
Int J Nanomedicine · 2026 · PMID 42131125 · Full text
Chronic pain management faces significant limitations due to adverse effects and insufficient long-term relief from existing therapies. Extracellular vesicles (EVs) are lipid bilayer-enclosed particles naturally carrying...
Chronic pain management faces significant limitations due to adverse effects and insufficient long-term relief from existing therapies. Extracellular vesicles (EVs) are lipid bilayer-enclosed particles naturally carrying proteins, nucleic acids, and metabolites. Recently, EVs have emerged as a potential alternative approach. This review examines EVs from mesenchymal stem cells, neural cells, macrophages, and gut microbiota. EV activity is then assessed across the three major pain types defined by the ICD‑11: nociceptive pain, neuropathic pain, and nociplastic pain. We elucidate how source-specific EVs dynamically regulate different kinds of pain through multi-modal mechanisms, including neural signal transduction, neuroimmune axis coordination, structural neural repair, and metabolic network reprogramming. Furthermore, we discuss how these inherent therapeutic properties can be augmented through engineering approaches such as surface modification and cargo encapsulation, which enhance targeting and payload delivery. By integrating mechanistic insights into source‑specific EV functions with emerging engineering strategies, this review may provide a rational framework for developing next‑generation EV‑based analgesics. We conclude that harnessing the innate biological properties of EVs, complemented by strategic engineering, represents a potential non-opioid strategy for precise and effective management of chronic pain.
A Nanomedicine Strategy: Spatiotemporally Programmed Delivery of Engineered Exosomes via Smart Scaffolds for Craniofacial Bone Regeneration.
Yang Q, Ran G, Jin H … +8 more , Zhai W, Lu J, Jiang W, Luo J, Fang S, Zhang Y, Liu H, Lin J
Int J Nanomedicine · 2026 · PMID 42131124 · Full text
The convergence of nanomedicine and regenerative biology offers new paradigms for tissue repair. The reconstruction of critical-sized bone defects, particularly within the anatomically intricate and physiologically disti...
The convergence of nanomedicine and regenerative biology offers new paradigms for tissue repair. The reconstruction of critical-sized bone defects, particularly within the anatomically intricate and physiologically distinct landscape of the craniomaxillofacial (CMF) region, represents a formidable frontier in regenerative medicine. Bone regeneration is not a singular biological event but a temporally orchestrated symphony, necessitating the precise, sequential coordination of immunomodulation, angiogenesis, and osteogenesis. While mesenchymal stem cell-derived extracellular vesicles (MSC-Exos) have emerged as a paradigm-shifting cell-free therapeutic - circumventing the engraftment instability, tumorigenicity, and immunogenicity limitations of live cell therapies-their clinical translation remains hindered by a fundamental kinetic mismatch: the delivery of a static, unmodulated bolus to a highly dynamic wound microenvironment. Current therapeutic strategies predominantly rely on simple injection or bulk incorporation of MSC-Exos into scaffolds. These static delivery paradigms fail to recapitulate the physiological rhythm of healing, often creating a kinetic mismatch between a single therapeutic cargo and the host's changing needs. This review bridges a critical synthesis gap by proposing a novel "spatiotemporal programming" framework for bone regeneration. We systematically integrate cargo engineering strategies (eg, hypoxic/inflammatory priming, genetic modification) with smart biomaterial design (eg, stimuli-responsive hydrogels, core-shell scaffolds) to achieve sequential, phase-specific delivery. By aligning exosomal bioactivity with the intrinsic immuno-angiogenic-osteogenic cascade and emphasizing cargo tailoring for craniomaxillofacial specificity, this work provides a translational roadmap for next-generation, precision-guided skeletal reconstruction.
A Photothermally Triggered Nanoplatform for Multidimensional Antibacterial Therapy and Accelerated Healing of Infected Wounds.
Fan Y, Li J, Wang P … +9 more , Peng Y, Yan C, Li X, Wang Z, Li X, He Z, Li W, Yin B, Jia C
Int J Nanomedicine · 2026 · PMID 42125089 · Full text
BACKGROUND: Bacterial infection and biofilm formation synergistically hinder wound healing by perpetuating inflammation and evading conventional treatments. Monotherapeutic strategies often fail to simultaneously eradica...
BACKGROUND: Bacterial infection and biofilm formation synergistically hinder wound healing by perpetuating inflammation and evading conventional treatments. Monotherapeutic strategies often fail to simultaneously eradicate resilient biofilms and rectify the dysregulated wound microenvironment. To overcome these limitations, we developed a multifunctional and targeted nanoplatform for synergistic antibacterial therapy and immunomodulation. METHODS: The smart nanoplatform (CCP-DFO(Fe)) was constructed with a triple-component architecture: a photothermal CuS core pre-loaded with chlorogenic acid (CGA), enveloped by a thermo-responsive poly(N-vinylcaprolactam) (PVCL) shell, and surface-functionalized with deferoxamine-iron (DFO(Fe)) via amide coupling for active bacterial targeting. RESULTS: The nanoplatform exhibits effective bacterial targeting via DFO(Fe)-mediated siderophore mimicry, enabling preferential accumulation at infection sites. Under NIR irradiation, CCP-DFO(Fe) nanoplatform exhibits efficient photothermal conversion, rapidly elevating the temperature to 44.3 °C within 4 min, which induces the sudden collapse of the PVCL shell from a uniform swollen state to a phase-separated state, leading to shell disruption and consequent exposure of the CGA-loaded CuS nanoparticles (CSC). Under physiological conditions, the CSC nanoplatform gradually releases Cu and CGA, which, together with the photothermal effect, synergistically exert potent antibacterial activity. As a result, the nanoplatform achieves highly effective bacterial eradication, reducing the survival rates of both and to below 5%, along with pronounced anti-biofilm activity. Beyond its antibacterial activity, the released CGA further exerts antioxidant and anti-inflammatory effects by scavenging reactive oxygen species and promoting macrophage polarization toward the pro-healing M2 phenotype, thereby facilitating inflammation resolution. In an infected rat wound model, CCP-DFO(Fe) combined with NIR irradiation achieved 98.56 ± 1.08% wound closure by day 14, with nearly complete bacterial eradication, while simultaneously promoting angiogenesis and collagen deposition. CONCLUSION: This integrated nanoplatform combines targeted antibacterial activity, biofilm disruption, and inflammation resolution into a single system, demonstrating significant potential for treating infected and chronic wounds.
Synergistic Neuroprotection of FeO Nanoparticles Combined with Intermittent Theta Burst Stimulation in Ischemic Stroke via Nrf2-Mediated Ferroptosis Regulation.
Huang YY, Gui LH, Yu WX … +8 more , Tao R, Zhu ZH, Li JJ, Zhao YN, Zhang XY, Zhang YZ, Liu Y, Bi X
Int J Nanomedicine · 2026 · PMID 42125088 · Full text
BACKGROUND: Ischemic stroke (IS) accompanied by reperfusion injury results from a cascade of events, including oxidative stress, inflammation, and neuronal apoptosis. Current therapies are limited by poor blood-brain bar...
BACKGROUND: Ischemic stroke (IS) accompanied by reperfusion injury results from a cascade of events, including oxidative stress, inflammation, and neuronal apoptosis. Current therapies are limited by poor blood-brain barrier (BBB) penetration and insufficient targeting efficiency. OBJECTIVE: This study developed an iTBS-FeO nanoparticle system to enhance magnetic targeting and explore its potential multi-pathway neuroprotective effects. METHODS: We constructed a therapeutic platform integrating intermittent theta burst stimulation (iTBS) with magnetic FeO nanoparticles. Targeting efficiency to the ischemic penumbra was assessed under magnetic guidance with or without iTBS. Potential mechanisms were evaluated by examining ferroptosis-related signaling (Nrf2/GPX4), mitochondrial membrane potential, and microglial polarization. iTBS was compared with conventional rTMS. RESULTS: iTBS significantly enhanced magnetic targeting, resulting in approximately threefold greater FeO enrichment in the penumbra compared with magnetic guidance alone. This enhanced accumulation was associated with a possible transient modulation of BBB permeability. The combined iTBS-FeO treatment produced synergistic neuroprotective effects, which were associated with activation of the Nrf2/GPX4 pathway, reduced ferroptosis-related markers, improvement of mitochondrial function, and modulation of microglial polarization toward an anti-inflammatory phenotype. Under the experimental conditions used, iTBS achieved approximately 35% higher targeting efficiency than rTMS. These effects were accompanied by improved functional recovery in rodent stroke models. CONCLUSION: The iTBS-FeO system represents a promising preclinical strategy for enhancing nanoparticle targeting and multi-pathway neuroprotection in ischemic stroke. Further studies are required to clarify the precise mechanisms underlying BBB modulation and to evaluate long-term safety and translational potential.
Tri-Functional MgTA@MnO Nanozymes Orchestrate Redox Defense, Angiogenesis, and Immunometabolism for Osteoporotic Bone Regeneration.
Gu Y, Li L, Shen Y … +7 more , Li Y, Wang Y, Wang Z, Wang K, Jiang S, Xu T, Yang M
Int J Nanomedicine · 2026 · PMID 42117121 · Full text
PURPOSE: In osteoporotic conditions, bone regeneration is hindered by a pathological triad: persistent oxidative stress, compromised vascularization, and a dysregulated osteoimmune microenvironment. The purpose of this...
PURPOSE: In osteoporotic conditions, bone regeneration is hindered by a pathological triad: persistent oxidative stress, compromised vascularization, and a dysregulated osteoimmune microenvironment. The purpose of this study was to engineer a multifunctional nanotherapeutic platform capable of orchestrating redox defense, angiogenesis, and immunometabolic reprogramming to accelerate bone repair. METHODS: We synthesized a tri-functional nanozyme (MgTA@MnO) featuring a metal-phenolic network (MPN) coating, established through the one-step coordination of tannic acid (TA) and magnesium ions (Mg⁺) onto manganese dioxide nanoparticles. For sustained local delivery, these catalytic nanomedicines were dispersed within a standard photocrosslinkable, injectable methacrylated gelatin (GelMA) matrix. The system's efficacy was evaluated across pre-osteoblast, endothelial, and macrophage cell models. Underlying immunomodulatory mechanisms were delineated using transcriptomic sequencing. Therapeutic outcomes were assessed in an ovariectomized (OVX) osteoporotic rat model bearing femoral bone defects. RESULTS: The localized nanozyme delivery system efficiently scavenged reactive oxygen species (ROS), protecting osteoblasts from oxidative damage by awakening the endogenous NRF2 defense pathway. The platform also robustly stimulated endothelial cell migration and tube formation. Crucially, Mg⁺ and TA synergized with the MnO core to drive precise macrophage reprogramming, shifting the population from a pro-inflammatory M1 state toward a pro-reparative M2 phenotype. Transcriptomic profiling revealed this immunometabolic transition was dictated by targeted suppression of the IL-17/MAPK/NF-κB inflammatory axis and concurrent activation of the STAT3/IL-10 cascade. Consequently, this optimized osteoimmune niche promoted osteogenesis while restraining osteoclastogenesis in vitro. In vivo evaluations confirmed excellent biosafety and demonstrated markedly accelerated, vascularized trabecular bone regeneration, correlating with robust M2 macrophage infiltration. CONCLUSION: By coupling catalytic ROS scavenging with targeted immunometabolic modulation, the MgTA@MnO nanotherapeutic system successfully remodels the hostile osteoporotic microenvironment. Utilizing a conventional hydrogel as a local vehicle, this tri-functional nanozyme approach provides a highly translatable paradigm for managing compromised bone fractures.
Plant-Derived Nanovesicles for Ischemic Stroke Therapy via the Gut Microbiota-Gut-Brain Axis: A New Paradigm of Systemic Regulation.
Jiang J, Yu F, He M … +5 more , Huang R, He H, Murong Z, Xiong S, Liu M
Int J Nanomedicine · 2026 · PMID 42117120 · Full text
Ischemic stroke (IS) is a globally significant disease with complex pathological mechanisms. Traditional therapeutic strategies centered on central nervous system-targeted delivery face substantial limitations due to the...
Ischemic stroke (IS) is a globally significant disease with complex pathological mechanisms. Traditional therapeutic strategies centered on central nervous system-targeted delivery face substantial limitations due to the presence of the blood-brain barrier (BBB) and the multifactorial nature of the disease. In recent years, the gut microbiota-gut-brain axis, which elucidates the multi-pathway dialogue between the gut and the brain, has provided a novel systemic intervention perspective for IS treatment. In this context, Plant-Derived Nanovesicles (PDNVs), a class of natural nanocarriers derived from plants, have emerged prominently due to their inherent multi-component synergistic properties, excellent biocompatibility, and cross-kingdom regulatory capabilities. Critically, IS itself rapidly induces gut dysbiosis and barrier disruption, creating a vicious cycle that amplifies neuroinflammation-a pathological feature shared with other inflammatory conditions such as colitis and Inflammatory bowel disease. In this context, PDNVs, a class of natural nanocarriers derived from plants, have emerged prominently due to their inherent multi-component synergistic properties, excellent biocompatibility, and cross-kingdom regulatory capabilities. Drawing on mechanistic insights from these related disease models, this article systematically discusses the multi-level integrated mechanism of PDNVs as novel "functional messengers", involving reshaping the gut microenvironment, mediating systemic metabolic-immune signals, and ultimately synergistically activating the central nervous repair network, thereby offering a new paradigm for IS therapy. This review not only summarizes the mechanisms of action of PDNVs but also systematically constructs a framework and strategy for their translation from experimental research to clinical application. Highlighting critical hurdles such as the need for standardized production and rigorous quality control to ensure batch-to-batch consistency.
Comparative in vitro Study on Immunomodulatory Effects of Nano-Hydroxpatite Powders on Human Immune Cells.
Grubczak K, Kretowska-Grunwald A, Szalaj U … +3 more , Starosz A, Swieszkowski W, Moniuszko M
Int J Nanomedicine · 2026 · PMID 42117119 · Full text
INTRODUCTION: Significant advancement was recently achieved in the field of hydroxyapatite nanoparticles, contributing to their implementation in numerous biomedical applications, including bone tissue reconstruction. Ne...
INTRODUCTION: Significant advancement was recently achieved in the field of hydroxyapatite nanoparticles, contributing to their implementation in numerous biomedical applications, including bone tissue reconstruction. Nevertheless, the influence of these materials on the immune system still remains an unresolved issue. MATERIALS: Here, we managed to reveal a direct in vitro impact of nano-hydroxyapatite particles on immunological, cellular and humoral components. Further, we analyzed the effect of nanoparticle size and shape on healthy human immune cells residing in the peripheral blood. Special attention was given to particles produced using the microwave hydrothermal synthesis method and precisely controlled size. Viability, phenotypes, activation status, cytokine production and release were assessed using flow cytometry and immunoenzymatic techniques. RESULTS: We showed that large-sized nanoparticles caused significant induction of immune response associated with innate and acquired immunity, in size-dependent manner. The synthesized nanoparticles allowed for avoidance of the immunogenicity, with no changes in inflammatory cytokines, supporting high biocompatibility. Various effects suggest a different potential use of examined nanoparticles, whether proinflammatory or neutral conditions are required in the field of anticancer therapy or transplantology respectively. DISCUSSION: Obtained results indicate that precise selection of nano-hydroxyapatites with specific immunomodulatory properties might be crucial for application in the clinical setting. Subsequent studies would establish most suitable therapeutic approaches where selected nano-hydroxyapatites could be implemented.
Lung-Targeted Lipid Nanoparticles Delivery of Wogonin for Pulmonary Fibrosis in Mice via Modulation of Cellular Proteostasis.
Wang L, Lin F, Gao F … +10 more , Jia Z, Liu J, Liu X, Shang J, Ru X, Zhao Y, Zhao T, Yang L, Guo Y, Zhang M
Int J Nanomedicine · 2026 · PMID 42117118 · Full text
INTRODUCTION: Pulmonary fibrosis (PF) is a chronic and progressive lung disease characterized by excessive scarring of lung tissue, ultimately leading to impaired pulmonary function and poor survival outcomes. Currently,...
INTRODUCTION: Pulmonary fibrosis (PF) is a chronic and progressive lung disease characterized by excessive scarring of lung tissue, ultimately leading to impaired pulmonary function and poor survival outcomes. Currently, effective treatment options remain limited, with lung transplantation being the only definitive therapy. Wogonin, a bioactive flavonoid derived from the traditional Chinese medicinal herb , has demonstrated potent anti-fibrotic effects in both in vitro and in vivo studies. However, its clinical application is hindered by poor tissue specificity, resulting in inadequate accumulation at fibrotic sites and low systemic bioavailability. METHODS: We developed a lung-targeted, wogonin-loaded lipid nanoparticle system (LNP-Wog). The stability and biocompatibility of LNP-Wog were systematically evaluated, and its anti-fibrotic efficacy was assessed in murine PF models. Proteomic analysis was conducted to identify key components of the LNP-associated "protein corona" responsible for lung targeting. Additionally, biotin-affinity pulldown assays combined with Gene Ontology (GO) enrichment analysis were performed to elucidate the underlying anti-fibrotic mechanisms of wogonin. RESULTS: LNP-Wog exhibited excellent stability, biocompatibility, and significant anti-fibrotic efficacy in murine PF models. Proteomic analysis revealed fibrinogen as a critical component of the LNP "protein corona", facilitating lung endothelial targeting through integrin-mediated interaction. Mechanistically, wogonin was found to localize to the endoplasmic reticulum, where it promotes proteostasis by inhibiting protein synthesis via enhanced phosphorylation of eIF2α, a key event in the integrated stress response. CONCLUSION: These findings underscore the therapeutic potential of lung-targeted LNP-Wog nanoparticles as a promising strategy for the treatment of pulmonary fibrosis.
The Effect of Aspirin Nanoemulsion on TNFα and iNOS in Gastric Tissue in Comparison with Conventional Aspirin [Retraction].
Int J Nanomedicine · 2026 · PMID 42111274 · Full text
[This retracts the article DOI: 10.2147/IJN.S86947.].
[This retracts the article DOI: 10.2147/IJN.S86947.].
Recent Advances in Antitumor Nanomedicine Based on Covalent Organic Frameworks.
Xu F, Wang R, Cheng Z … +2 more , Zhang Z, Tian J
Int J Nanomedicine · 2026 · PMID 42111273 · Full text
Cancer remains one of the leading threats to human health today. With the rapid advancement of nanotechnology, the integration of nanomaterials with therapeutic strategies has shown great potential in addressing the limi...
Cancer remains one of the leading threats to human health today. With the rapid advancement of nanotechnology, the integration of nanomaterials with therapeutic strategies has shown great potential in addressing the limitations of conventional cancer treatments. Covalent organic frameworks (COFs) are novel crystalline porous polymers with well-defined backbones and nanopores, mainly composed of light elements (H, B, C, N, and O) linked by dynamic covalent bonds. Owing to their tunable morphology, adjustable porosity, intelligent responsive release, and good biocompatibility, COFs have been extensively explored for applications in cancer diagnosis and treatment. This review summarizes recent progress in the synthesis of COFs, their distinctions from other traditional nanomaterials, their tumor microenvironment-responsive release capabilities, and highlights the development of multifunctional COF-based nanoplatforms for cancer imaging and treatment. Finally, the prospects and challenges of COF-based nanoplatforms in tumor therapeutics are discussed, aiming to provide new diagnostic and therapeutic strategies for subsequent tumor prevention and treatment.
Biomaterials Promote the Regression of Atherosclerotic Plaque by Regulating Cell Behavior.
Wang C, Sun C, Wu X … +3 more , Ding Z, Liu K, Cao J
Int J Nanomedicine · 2026 · PMID 42099533 · Full text
Atherosclerosis is characterized by the deposition of lipid within arterial walls, precipitating the initiation and progression of atherosclerotic lesions. Over time, these plaques enlarge and rupture, initiating thrombo...
Atherosclerosis is characterized by the deposition of lipid within arterial walls, precipitating the initiation and progression of atherosclerotic lesions. Over time, these plaques enlarge and rupture, initiating thrombosis cascades that pose significant risks to patient safety. Conventional therapies, including 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (eg, statins) and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, predominantly target lipid reduction while overlooking the intricate microenvironment within atherosclerotic plaque. Statins possess limited lipid-lowering efficacy and may even exhibit insensitivity or intolerance in patients. While PCSK9 inhibitors, as adjuvant therapy, demonstrate potent lipid-lowering effects, they fail to further stabilize vulnerable plaques. In contrast, biomaterials have emerged as pivotal tools for addressing unstable plaques. By restoring endothelial cell (EC) function, inhibiting neutrophil activation, modulating macrophage behavior, and preventing the phenotypic transformation of smooth muscle cells, biomaterials effectively promote plaque regression. This review explores the pathogenesis of atherosclerosis and highlights recent advancements in biomaterial-based therapies for vulnerable plaques, aiming to offer novel insights and solutions to this pressing global health challenge.
How Advanced is Nanomedicine to Treat Atherosclerosis? A Comprehensive Review of the Literature.
Zhang J, Tong J, Sun Y … +5 more , Sun J, Gao R, Sun D, Guo X, Wei Y
Int J Nanomedicine · 2026 · PMID 42094740 · Full text
Atherosclerosis (AS) is a major underlying cause of cardiovascular disease. Rupture of unstable atherosclerotic plaques can induce severe acute cardiovascular events and sudden cardiac death. Therefore, developing target...
Atherosclerosis (AS) is a major underlying cause of cardiovascular disease. Rupture of unstable atherosclerotic plaques can induce severe acute cardiovascular events and sudden cardiac death. Therefore, developing targeted interventional therapies for atherosclerotic plaques is clinically important to improve cardiovascular mortality. With the advancement of nanomedicine, nanomaterials have demonstrated great potential in atherosclerosis treatment due to their unique compositional/structural features, synthesis strategies, and surface modifications. Based on the pathological characteristics of atherosclerotic plaques, the design and preparation of stimulus-responsive, surface-functionalized, and conditionally-released nanomaterials have become an important approach to achieving precise intervention for atherosclerotic lesions. Considering the pathological features of different cell types involved in AS progression, this review describes the targeting strategies, structural and functional designs, and potential mechanisms of action of targeted nanotherapies in the treatment of atherosclerosis. By summarizing representative recent studies in detail, we reveal the intrinsic interactions and relationships between current targeted nanotherapies and atherosclerotic plaques. Finally, this review provides an outlook on the future application of nanomaterials by presenting key scientific questions that have not yet been addressed, to advance the clinical translation of targeted nanotherapies for atherosclerosis.
Heparin-Conjugated Silver Nanoparticles via Amide Chemistry for Selective Targeting of Triple-Negative Breast Cancer and Pathogenic Fungi.
Ahire JH, Wang Q, Bao Y … +4 more , Storer ISR, Bidula S, Rowley G, Crack JC
Int J Nanomedicine · 2026 · PMID 42094739 · Full text
BACKGROUND: Heparin, a polydisperse glycosaminoglycan, is well-known for its anticoagulant activity and clinical use in preventing venous thromboembolism. In addition to coagulation, heparin and its derivatives have show...
BACKGROUND: Heparin, a polydisperse glycosaminoglycan, is well-known for its anticoagulant activity and clinical use in preventing venous thromboembolism. In addition to coagulation, heparin and its derivatives have shown therapeutic potential in cancer and infectious, inflammatory, and neurodegenerative diseases. This study aimed to develop and evaluate heparin-capped AgNPs (hep-AgNPs) as multifunctional nanotherapeutics with selective cytotoxicity, antibacterial, and antifungal activity. METHODS: Heparin was covalently conjugated to cysteamine-terminated silver nanoparticles via MES-buffer-mediated amide coupling, providing a mild, aqueous alternative to conventional DMF-based methods. The nanoparticles were characterised by UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), dynamic light scattering (DLS), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) analyses. The colloidal stability was assessed over a broad range of pH values. The biological performance of hep-AgNPs was evaluated in vitro against a triple-negative breast cancer (TNBC) cell line (MDA-MB-231), a double-positive cell line (MCF-7), and normal breast cells (MCF-10A), and microbial strains, including , and . RESULTS: The synthesised hep-AgNPs exhibited high yield, effective heparin surface functionalization, and excellent colloidal stability at physiological pH, with stability systematically assessed across a broad pH range. Hep-AgNPs demonstrated time and concentration-dependent selective cytotoxicity, toward breast cancer cells, including MCF-7 and triple-negative MDA-MB-231, with a favourable selectivity index (>1) compared to MCF-10A cells, and the strongest selectivity observed in the TNBC model at 48 h. In addition, hep-AgNPs showed potent antibacterial activity (IC = 24.3 µg/mL) and antifungal activity (IC = 6.2 µg/mL for and 24.43 µg/mL for ). In addition, they exhibit strong biocompatibility with keratinocytes and fibroblasts. CONCLUSION: Heparin-capped silver nanoparticles combine the biological functionality of heparin with the antimicrobial and selective cytotoxic properties of the silver nanoparticles. Their selective cytotoxicity, antimicrobial efficacy, and favourable cellular interaction profiles highlight their potential as multifunctional nanoplatforms for applications such as chronic wound management in neutral to alkaline wound environments, and dose-controlled, targeted therapeutic strategies relevant to aggressive cancer models, including TNBC.
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