International Journal Of Nanomedicine[JOURNAL]
Sun
200 papers
Application and Future Perspectives of Extracellular Vesicle-Loaded Scaffold in Spinal Cord Injury.
Zhang W, Chai X, Xu N … +4 more , Ma W, Zhou Y, Lou X, Yang H
Int J Nanomedicine · 2026 · PMID 42371509 · Full text
Following the initial trauma of spinal cord injury (SCI), the secondary injury phase-characterized by inflammation, oxidative stress, neuronal death, and axonal demyelination-establishes an adverse microenvironment that...
Following the initial trauma of spinal cord injury (SCI), the secondary injury phase-characterized by inflammation, oxidative stress, neuronal death, and axonal demyelination-establishes an adverse microenvironment that hinders functional recovery. Despite the availability of existing clinical therapies, they often yield suboptimal functional recovery. In this review, the applications and future prospects of extracellular vesicle (EV)-loaded scaffolds for SCI repair are summarized. This review discusses the biological properties and therapeutic action of EVs, as well as limitations of using them as a single agent, such as rapid clearance and poor targeting. Other scaffold loading strategies and types that change in response to the microenvironment are also reviewed. This review highlights the advancement of EV-loaded scaffolds in alleviating secondary injury, controlling inflammation, enhancing neural regeneration and remyelination, and promoting angiogenesis. Microvesicles, a high-capacity and large subtype of EVs with rapid release and functional surface proteins, in particular, have been shown to have multi-target repair capabilities in various disease models. Their integration with scaffolds for SCI is suggested as a promising translational direction. Current challenges encompass subtype standardization, safety evaluation, as well as large-scale production. The review concludes that EV-loaded scaffolds are not just delivery systems, but a regenerative platform that enables spatiotemporal structure-signal synergy. Subtype-specific selection, pathology-stage-directed release, and industry-compliant quality control should be the focus in future studies to develop this strategy beyond basic research into clinical translation.
Identification of Bone Marrow and Peripheral Blood Plasma Extracellular Vesicle Protein Biomarker Signatures for Multiple Myeloma Diagnosis and Staging.
Cheryl A, Sheridan R, Brennan K … +5 more , Bazou D, Matallanas D, O'Gorman P, Iglesias-Martinez LF, Mc Gee MM
Int J Nanomedicine · 2026 · PMID 42371508 · Full text
PURPOSE: Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of abnormal plasma cells within the bone marrow (BM). Despite advances in treatment that have improved survival, the...
PURPOSE: Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of abnormal plasma cells within the bone marrow (BM). Despite advances in treatment that have improved survival, the disease remains incurable. MM diagnosis requires invasive bone marrow biopsy to quantify the percentage of malignant plasma cells. In this study, the potential of extracellular vesicles (EVs) as a non-invasive liquid biopsy for MM diagnosis and staging was investigated, highlighting the diagnostic value of their proteomic biomarker cargo. PATIENTS AND METHODS: Plasma-derived EVs from peripheral blood and bone marrow of 33 MM patients and 12 healthy donors were isolated, and their proteomic content was profiled via mass spectrometry. Biomarker signatures were identified using supervised machine learning to predict monoclonal gammopathy of undetermined significance (MGUS), progression to symptomatic MM, and relapse. Their discriminatory power was further evaluated through receiver operating characteristic curve analysis, and complementary performance metrics, including accuracy, sensitivity, specificity, predictive values, and F1 score. Significantly altered proteins were additionally assessed for functional enrichment in relevant biological pathways. RESULTS: The analysis identified a six-protein biomarker signature, forming four optimal logistic regression diagnostic MM peripheral blood models with predictive accuracies of >85% and areas under the curve of >0.91. The signature was characterized by increased abundance of APOC1 and LGALS1 and decreased abundance of S100A7, CD226, ALAD, and KRT78, reflecting immune modulation, impaired immune surveillance, and disrupted proteostatic pathways. CONCLUSION: The performance of the identified proteins supports their potential as a minimally invasive EV-based liquid biopsy in MM diagnosis and monitoring, warranting future validation.
Se-Fe Hydrogel with Switchable Hyperthermia for Osteosarcoma Therapy.
He J, Miu J, Ning C … +2 more , Ning S, Wei Q
Int J Nanomedicine · 2026 · PMID 42368405 · Full text
INTRODUCTION: Clinical treatment of osteosarcoma remains challenging because of residual tumor-associated recurrence, bacterial infection, and insufficient bone reconstruction. To address these challenges, a selenium-iro...
INTRODUCTION: Clinical treatment of osteosarcoma remains challenging because of residual tumor-associated recurrence, bacterial infection, and insufficient bone reconstruction. To address these challenges, a selenium-iron Prussian blue nanocube (FeSePB) was designed and encapsulated within a thermoresponsive hydrogel for osteosarcoma therapy. METHODS: The FeSePB nanocube functions as an efficient photothermal conversion agent, producing localized heating under near-infrared (NIR) irradiation and enabling controlled softening of the hydrogel after implantation under laser irradiation. Following administration into the osteosarcoma site, initial NIR irradiation triggered hydrogel softening and rapid release of FeSePB, resulting in elevated local temperature that eliminated residual tumor cells and achieved antibacterial effects through photothermal therapy (PTT). Concurrent selenium release further inhibited bacterial growth, reducing infection risk. RESULTS: In vitro experiments demonstrated that sustained mild PTT induced moderate hyperthermia, which supported bone regeneration. In vivo animal experiments demonstrated remarkable tumor growth inhibition, with inhibition rates of about 90.67% compared with the control group. Thus, the FeSePB hydrogel demonstrated NIR-switchable temporal regulation, enabling integrated anti-tumor, anti-infective, and pro-osteogenic functions during osteosarcoma treatment. CONCLUSION: This strategy offers a multifunctional therapeutic platform that simultaneously addresses tumor proliferation, infection, and bone loss, highlighting its potential for clinical translation.
A Brain-Targeted Organophosphorus Hydrolase Fusion Protein Mediated by Angiopep-2 Neutralizes Central Organophosphates and Alleviates Neurotoxicity.
Xie Y, Zhai Y, Shang J … +7 more , Ma M, Wang D, Xu S, Ran Y, Li Z, Gao X, Gao J
Int J Nanomedicine · 2026 · PMID 42368404 · Full text
PURPOSE: Organophosphates (OPs) exert neurotoxicity by inhibiting acetylcholinesterase (AChE) activity, leading to acetylcholine accumulation, excessive nervous system stimulation, and even fatal outcomes. Current clinic...
PURPOSE: Organophosphates (OPs) exert neurotoxicity by inhibiting acetylcholinesterase (AChE) activity, leading to acetylcholine accumulation, excessive nervous system stimulation, and even fatal outcomes. Current clinical countermeasures focus on AChE reactivation and symptom antagonism but lack the ability to efficiently clear OPs in vivo, especially in the brain, failing to mitigate central neurotoxicity and resulting in persistent neuronal damage and permanent disability in survivors. Organophosphorus hydrolase (OPH) has robust OP clearance capacity but is hindered by poor blood-brain barrier (BBB) penetration. Thus, the purpose of this study is to address the BBB penetration challenge of OPH and develop an effective strategy for efficient clearance of brain-invading OPs to improve the prognosis of patients with OP-induced central neurotoxicity. PATIENTS AND METHODS: A fusion protein ANG-OPHDS5 was constructed by conjugating OPH mutant OPHDS5 with Angiopep-2 (ANG), a brain-targeting ligand that mediates transcytosis across the BBB via specific binding to low-density lipoprotein receptor-related protein 1 (LRP1). In vivo imaging and pharmacodynamic studies were performed to evaluate the brain-targeting ability, OP clearance efficiency, and neurotoxicity alleviation effect of ANG-OPHDS5. RESULTS: In vivo imaging and pharmacodynamic studies confirmed that the constructed fusion protein ANG-OPHDS5 efficiently achieved targeted delivery to the brain, effectively cleared OPs residing in the central nervous system (CNS), and significantly alleviated neurotoxicity induced by OPs. CONCLUSION: Our strategy of centrally targeted delivery of OPH-based bioscavengers (ANG-OPHDS5) overcomes the limitations of current OP poisoning treatments, which lack efficient brain OP clearance capacity. This strategy holds great potential for improving the prognosis of patients with OP-induced central neurotoxicity.
PEG-NH-Modified Gold Nanoparticle Deliver miRNA-140 for Effective Treatment of Osteoarthritis.
Luo X, Jiang X, Kang Z
Int J Nanomedicine · 2026 · PMID 42368403 · Full text
BACKGROUND: Osteoarthritis is a prevalent disease that causes pain and disability in older adults. MicroRNA-140 (miR-140) emerges as a promising therapeutic agent as it suppresses cartilage-degrading enzymes (eg, ADAMTS5...
BACKGROUND: Osteoarthritis is a prevalent disease that causes pain and disability in older adults. MicroRNA-140 (miR-140) emerges as a promising therapeutic agent as it suppresses cartilage-degrading enzymes (eg, ADAMTS5, MMPs). However, its clinical translation is limited by rapid intra-articular degradation and poor chondrocyte penetration. The purpose of this experiment was to construct a nanocarrier for delivering miR-140 into chondrocytes, and to detect its delivery efficiency and biological effects. METHODS: We engineered polyethylene glycol-aminated gold nanoparticles (AuNPs-PEG-NH) for miR-140 delivery. The efficiency of AuNPs-PEG-NH-mediated miR-140-5p (AuNPs-miR-140) delivery was assessed by fluorescence microscopy and flow cytometry. The biological function of AuNPs-miR-140 complexes was detected by quantitative real-time polymerase chain reaction (RT-qPCR), Western blot, and enzyme-linked immunosorbent assay. The effect of AuNPs-miR-140 in attenuating osteoarthritis progression was tested in a mouse model. RESULTS: Fluorescence microscopy and flow cytometry revealed efficient delivery of miR-140-5p into ATDC5 cells by AuNPs-PEG-NH. RT-qPCR analysis demonstrated a controlled sustained release of miR-140-5p from the nanocarriers, maintaining elevated miR-140-5p levels for 14 days. In vitro, AuNPs-miR-140 significantly suppressed catabolic factors (MMP-13 and ADAMTS5; <0.01) and upregulated anabolic markers (COL2 and ACAN; <0.01) in IL-1β-stimulated chondrocytes. Consistent with these findings, in vivo studies showed that AuNPs-miR-140 significantly attenuated cartilage degradation in mice with osteoarthritis, and preserved cartilage structural integrity. CONCLUSION: AuNPs-PEG-NH is an efficient intra-articular miRNA delivery platform that successfully overcame the critical limitations of free miRNA therapy. This system effectively restored cartilage homeostasis and delayed osteoarthritis progression by prolonging miR-140 bioactivity and promoting chondrocyte uptake.
The Current Application Prospects of Nanomedicine in Renal Ischemia-Reperfusion Injury.
Jiang C, Liu C, He X … +2 more , Guo Y, Zhang J
Int J Nanomedicine · 2026 · PMID 42368402 · Full text
Renal ischemia-reperfusion injury (RIRI) is one of the main causes of acute kidney injury (AKI), and its pathological mechanism is complex, mainly involving multiple pathological processes such as oxidative stress outbre...
Renal ischemia-reperfusion injury (RIRI) is one of the main causes of acute kidney injury (AKI), and its pathological mechanism is complex, mainly involving multiple pathological processes such as oxidative stress outbreak, uncontrolled inflammatory response, abnormal cell apoptosis, and microcirculatory disorders. Currently, there is a lack of efficient and accurate diagnosis and treatment strategies in clinical practice. As a cross discipline integrating nanomaterials, medicine and biology, nanomedicine has shown unique advantages and broad application prospects in the diagnosis and treatment field of RIRI in recent years. Its core carriers include inorganic nanoparticles, polymeric nanoparticles, nanoenzymes, extracellular vesicles, cell membrane camouflage nanoparticles and injectable nanohydrogels. The diagnosis and treatment system based on nanomedicine can breakthrough the limitations of traditional diagnosis and treatment models, and play an important role in early accurate diagnosis, targeted drug delivery, precise treatment of lesion sites, and prolonged drug circulation time in RIRI. It effectively solves pain points such as strong toxicity, short circulation time, and poor targeting of single drugs. However, the specific mechanism of action of nanomedicine in RIRI has not been fully elucidated, and issues such as the biosafety, in vivo metabolic patterns, and clinical translation bottlenecks of nanomedicine still need to be urgently addressed. This review aims to systematically review the application and mechanism research progress of nanomedicine in RIRI, briefly explain the core pathological mechanism of RIRI, focus on the application effects and mechanisms of nanomedicine systems composed of different types of nanocarriers in RIRI diagnosis and treatment, summarize the current research challenges and look forward to future development directions, providing theoretical basis and practical reference for in-depth research, technological breakthroughs, and clinical translation of nanomedicine in the field of RIRI.
Trivalent mRNA-LNP Vaccine Induces Robust Humoral and Cellular Immunity in Mice: Preclinical Evaluation for Porcine Enteric Coronaviruses.
Wang X, Li C, Wang S … +7 more , Liu C, Shi J, Xu W, Zhou S, Xu S, Shang Y, Li J
Int J Nanomedicine · 2026 · PMID 42368401 · Full text
INTRODUCTION: Porcine enteric coronaviruses (PECs) often co-infect swine, leading to high mortality, which underscores the need for multivalent vaccines. METHODS: A trivalent mRNA vaccine was formulated using SM-102 lipi...
INTRODUCTION: Porcine enteric coronaviruses (PECs) often co-infect swine, leading to high mortality, which underscores the need for multivalent vaccines. METHODS: A trivalent mRNA vaccine was formulated using SM-102 lipid nanoparticles (LNPs) and encodes PEDV-S, PDCoV-S, and TGEV-S in a single transcript. BALB/c mice were immunized intramuscularly with escalating doses (5, 10, 15, and 20 µg). Systemic IgG, mucosal IgA, neutralizing antibodies, cytokine profiles (IFN-γ, IL-4), and splenocyte proliferation were assessed. Monovalent formulations and commercial vaccines (PEDV/TGEV bivalent inactivated vaccine from Qilu Animal Health; PDCoV inactivated vaccine from Wuhan Keqian) served as controls. Data are mean ± SD (n = 5); one-way ANOVA with multiple comparisons was applied (* < 0.05; ** < 0.01; *** < 0.001). RESULTS: A moderate dose (10 µg) induced systemic IgG, IFN-γ, IL-4, and splenocyte proliferation, indicating activation of both Th1 and Th2 responses. Higher dose (15 µg) preferentially enhanced mucosal IgA and neutralizing antibody responses, exceeding those induced by commercial vaccines, suggesting potential improvement in mucosal protection. Monovalent SM-102-LNP formulations also elicited robust immune responses, approaching commercial benchmarks. DISCUSSION: This trivalent mRNA-LNP vaccine provides broad and potent humoral and cellular immunity in mice, supporting its potential as a platform for porcine vaccination. These results provide preclinical proof-of-concept, and further evaluation in swine is required to assess vaccine efficacy.
Advances in Nanotechnology-Based Immunomodulatory Strategies for the Treatment of Allergic Rhinitis.
Liu X, Zhao W
Int J Nanomedicine · 2026 · PMID 42368400 · Full text
Allergic rhinitis is a prevalent, chronic airway inflammatory disorder that poses growing public health, clinical, and socioeconomic challenges on a global scale. Allergen immunotherapy (AIT) is currently the only etiolo...
Allergic rhinitis is a prevalent, chronic airway inflammatory disorder that poses growing public health, clinical, and socioeconomic challenges on a global scale. Allergen immunotherapy (AIT) is currently the only etiological therapy that can modify the natural course of allergic rhinitis. However, conventional AIT has limitations such as significant individual differences in efficacy, long treatment duration, and local adverse effects. The above bottlenecks highlight the urgent need to develop precise, efficient, and more secure immune-targeted intervention strategies. In recent years, nanodurgs have opened a new avenue for allergic rhinitis immunotherapy by leveraging unique advantages such as precise drug release control, targeted delivery, and enhanced immunomodulation. This article systematically reviews the recent advances in nanotechnology-based immunotherapeutic strategies for allergic rhinitis, with particular emphasis on two innovative strategies: nanovaccines and nanobodies. We further discusses the utility of diverse nanocarrier platforms, including polymeric nanoparticles, liposomes, and exosomes, which as immunomodulatory adjuvants and precision delivery systems. In addition, we elucidate the design principles and mechanistic underpinnings of intelligent responsive nanosystems, highlighting their potential to concurrently improve therapeutic efficacy and safety through synergistic immunoregulation. Collectively, this review provides a scientific foundation for the future development of novel, clinically translatable interventions for immune-mediated diseases, including allergic rhinitis.
Advances in the Targeted Drug Delivery System for Renal Fibrosis.
Zheng YY, Hao JF, Liu JY … +4 more , Wang SY, Mu XD, Jiang HL, He YJ
Int J Nanomedicine · 2026 · PMID 42358463 · Full text
Renal fibrosis represents the ultimate outcome of almost all chronic kidney diseases (CKD), and is the primary cause of end-stage renal disease, making it a serious global health burden. Despite numerous preclinical drug...
Renal fibrosis represents the ultimate outcome of almost all chronic kidney diseases (CKD), and is the primary cause of end-stage renal disease, making it a serious global health burden. Despite numerous preclinical drugs demonstrating potential in the treatment of renal fibrosis, the majority fail to fulfill the stringent criteria for clinical applications. Key hurdles in renal fibrosis therapy not only involve intricate signaling networks and fibrosis-perpetuating microenvironments, complex renal structures, and pathological barriers, but also restrict drug delivery to lesions. Therefore, recent delivery system focused on co-delivering multiple drugs via nanoplatforms and functionalized with targeting ligands. These systems enable precise drug delivery to key effector cells in fibrosis (eg, myofibroblasts and tubular epithelial cells), thereby achieving targeted and highly effective therapy. This review summarizes the signaling pathways of renal fibrosis using the concept of the fibrosis niche and critically evaluates both drug delivery barriers and emerging targeted drug delivery system (TDDS). Furthermore, the potential challenges and future directions of TDDS for reversing renal fibrosis are discussed with the aim of providing guidance for the development of new therapeutic strategies.
Nanostructured Lipid Carriers Co-Loaded with Doxycycline, Gentamicin, and Thymol for Enhanced Intracellular Antibacterial Activity Against .
Morovati Moez N, Arabestani MR, Taheri M … +4 more , Karami P, Alikhani MY, Kazemi S, Hosseini SM
Int J Nanomedicine · 2026 · PMID 42358462 · Full text
BACKGROUND: Brucellosis is a zoonotic infection caused by spp. which persist within macrophages and complicate treatment. This study developed nanostructured lipid carriers (NLCs) co-loaded with doxycycline, gentamicin,...
BACKGROUND: Brucellosis is a zoonotic infection caused by spp. which persist within macrophages and complicate treatment. This study developed nanostructured lipid carriers (NLCs) co-loaded with doxycycline, gentamicin, and thymol to enhance intracellular delivery and antibacterial activity against . METHODS: Drug-loaded NLCs were prepared using high-shear homogenization followed by sonication. The formulations were characterized in terms of particle size, polydispersity index (PDI), zeta potential, morphology by FE-SEM, encapsulation efficiency, and in vitro drug release profile. Cytotoxicity was assessed using the MTT assay on J774A.1 macrophage. Antibacterial activity and intracellular efficacy against were evaluated using microbiological and cell-based assays. RESULTS: The optimized formulation showed a size of 398 ± 30 nm, PDI 0.35, and zeta potential -17.5 mV, with 97% encapsulation efficiency and stable morphology over nine months. The system exhibited sustained release up to 95% at 80 h, in contrast to rapid diffusion from free drugs. Intracellular studies showed that Gen-Dox-Thy@NLC achieved a 3.4-log reduction in bacterial load, demonstrating significantly higher efficacy (~1.6-log greater reduction) compared with free drugs (p < 0.05), while maintaining macrophage viability above 85%. CONCLUSION: The co-loaded NLC formulation provided controlled drug release, improved intracellular delivery, and enhanced antibacterial activity against . These findings suggest that Gen-Dox-Thy@NLC may serve as a promising candidate for brucellosis treatment and warrants further in vivo studies.
Cyclam-Modified Polyethyleneimine for Simultaneous TGFβ siRNA Delivery and CXCR4 Inhibition for the Treatment of CCl-Induced Liver Fibrosis [Retraction].
Int J Nanomedicine · 2026 · PMID 42344851 · Full text
[This retracts the article DOI: 10.2147/IJN.S314367.].
[This retracts the article DOI: 10.2147/IJN.S314367.].
Comparable Efficacy of Chitosan/miR-200b-3p and Lipofectamine/miR-200b-3p Delivered by Pluronic F127 Hydrogel to Facilitate Diabetic Wound Healing.
Lo WY, Chen CJ, Sin CH … +3 more , Hsu HC, Li ZX, Wang HJ
Int J Nanomedicine · 2026 · PMID 42338902 · Full text
BACKGROUND: The clinical application of miRNA therapeutics in diabetic foot ulcers (DFUs) is limited by the rapid degradation of miRNAs. We previously reported that topical lipofectamine (Lipo)-based miR-200b-3p delivery...
BACKGROUND: The clinical application of miRNA therapeutics in diabetic foot ulcers (DFUs) is limited by the rapid degradation of miRNAs. We previously reported that topical lipofectamine (Lipo)-based miR-200b-3p delivery by Pluronic F127 (PF127) hydrogel has pro-healing properties in diabetic wounds. However, Lipo's high cost and cytotoxicity concerns impede its clinical use. Chitosan (CS) is an inexpensive biopolymer. We investigated whether the topical delivery of PF127+CS+miR-200b-3p can accelerate wound healing in diabetic mice. METHODS: In vitro experiments were conducted, including the CCK-8 assay, gelation time measurement, scanning electron microscopy, Zetasizer Nano ZS analysis, release kinetics, swelling ratio, gel retardation assay, and uptake assay. In vivo experiments were performed on db/db mice with two 8 mm dorsal wounds. Four treatment groups including PF127, PF127+CS+miR-negative control (miR-NC), PF127+CS+miR-200b-3p, and PF127+Lipo+miR-200b-3p were examined. On day 14, skin tissues were harvested for H&E and immunohistochemical staining, as well as real-time PCR of variable genes and miR-200b-3p. RESULTS: The CCK-8 assay revealed the non-toxicity of CS on HaCaT keratinocytes. Furthermore, PF127 concentration-dependently decreased the positive surface charge of the CS/miR-200b-3p nanoparticles. The PF127 kept the diameter of the CS/miR-200b-3p nanoparticles at roughly 200-250 nm. In vivo gene expression confirmed that CS and Lipo had comparable transfection efficacy. Both the PF127+CS+miR-200b-3p and PF127+Lipo+miR-200b-3p groups accelerated wound healing compared to the PF127+CS+miR-NC group. The superb healing properties of the PF127+CS+miR-200b-3p group were supported by the expression levels of genes (, and ) and proteins (CD68, CD31, and γH2AX), which showed no significant differences between the PF127+CS+miR-200b-3p and PF127+Lipo+miR-200b groups. CONCLUSION: Topical delivery of CS/miR-200b-3p nanoparticles using PF127 is a promising treatment for diabetic wound healing. Our findings demonstrate that chitosan serves as a cost-effective, non-toxic alternative to Lipofectamine in diabetic wound management.
Reprogramming Metabolism and Immunity: Nanotechnology's Promise for Hepatocellular Carcinoma Precision Therapy.
Cheng M, Ni Y, Zhang W … +1 more , Wu Q
Int J Nanomedicine · 2026 · PMID 42338901 · Full text
The treatment of hepatocellular carcinoma (HCC) faces multiple dilemmas, including limited applicability of local therapy, easy development of resistance to targeted drugs, and low response rate to immune checkpoint inhi...
The treatment of hepatocellular carcinoma (HCC) faces multiple dilemmas, including limited applicability of local therapy, easy development of resistance to targeted drugs, and low response rate to immune checkpoint inhibitors (ICIs). The core crux lies in the "metabolic reprogramming-immune suppression" vicious cycle and tumor heterogeneity. This review aims to clarify the crosstalk between metabolic reprogramming and immune suppression in HCC, and summarize the design principles of nanoplatforms for synchronous intervention in metabolism and immunity. Nanotechnology, with core advantages of precise targeting, tumor microenvironment responsiveness, and multifunctional synergy, enables targeted regulation of glucose, fatty acid, and amino acid metabolic pathways. It synergizes with ICIs and local therapies to reshape the immunosuppressive microenvironment, and the "metabolic subtype-nanocarrier" matching strategy shows promising clinical potential. Current applications face challenges in carrier performance, personalized strategies, and clinical translation. Future development focusing on carrier optimization, multi-omics-based subtype matching, and standardized evaluation systems will promote nanotechnology to evolve from "broad-spectrum regulation" to "precise adaptation", providing a core tool for overcoming HCC treatment bottlenecks and advancing precision therapy.
Glucan-Based Nanoparticles Empower Precision Cancer Immunotherapy: Design Strategies, Immune Reprogramming Mechanisms, and Clinical Translation Prospects.
Xie Y, Zeng B, Li X … +7 more , Xu Q, Zhang Y, Sun L, Chang J, Wang Z, Zhu J, Yan X
Int J Nanomedicine · 2026 · PMID 42338900 · Full text
Tumor immunotherapy presents new opportunities for sustained tumor control by reinstating immune surveillance. However, its clinical efficacy is significantly limited by the immunosuppressive nature of the tumor microenv...
Tumor immunotherapy presents new opportunities for sustained tumor control by reinstating immune surveillance. However, its clinical efficacy is significantly limited by the immunosuppressive nature of the tumor microenvironment, considerable variability in patient responses, and the delicate balance required between immune activation and systemic toxicity. Recently, glucan-based nanoparticles have gained prominence as engineered platforms in precision tumor immunotherapy due to their favorable biocompatibility, programmable structural design, and inherent immune recognition capabilities. Comprehensive research has shown that these nanosystems not only facilitate the precise delivery of tumor antigens, immunoadjuvants, and immunomodulatory agents but also modulate the tumor immune microenvironment at various levels. These nanoparticles specifically target antigen-presenting cells, reprogram tumor-associated macrophages' phenotypes, reduce the function of immunosuppressive cells, and synergistically activate both innate and adaptive immune responses, significantly boosting antitumor immunity. This review methodically examines the principal strategies in the structural design and surface functionalization of glucan-based nanoparticles, with a focus on the molecular and cellular mechanisms of immune remodeling. It further highlights recent progress in their combined use with various immunotherapeutic modalities, such as immune checkpoint inhibitors, photodynamic or photothermal therapies, and cell-based treatments. Moreover, drawing on current preclinical studies and early clinical data, this article offers a comprehensive evaluation of the translational challenges these systems face, including long-term safety, scalable production, and regulatory issues. Overall, glucan-based nanoparticles are transitioning from traditional delivery systems to versatile therapeutic platforms that play a crucial role in immune regulation. They offer significant potential for novel theoretical frameworks and technological advances in the development of more precise, effective, and sustainable tumor immunotherapy strategies.
Ion‑Responsive in situ Gel of Quercetin‑Loaded PEGylated Liposomes for Anti‑inflammatory Treatment of Dry Eye Disease.
Yao X, He X, Liang Z … +5 more , Dong F, Zhang Z, Pu G, Ye J, Zhou T
Int J Nanomedicine · 2026 · PMID 42338899 · Full text
BACKGROUND: Dry eye disease (DED) is a global health burden with limited effective and safe treatments. Quercetin (Qu) possesses potent anti-inflammatory and antioxidant activities, but its poor solubility and short half...
BACKGROUND: Dry eye disease (DED) is a global health burden with limited effective and safe treatments. Quercetin (Qu) possesses potent anti-inflammatory and antioxidant activities, but its poor solubility and short half-life restrict ophthalmic use. METHODS: Qu‑loaded PEGylated liposomes (Qu‑PL) were prepared by thin‑film hydration and incorporated into gellan gum to form an ion‑responsive in situ gel (Qu‑PL‑ISG). The formulation was characterized for particle size (PS), zeta potential (ZP), polydispersity index (PDI), encapsulation efficiency (EE), short-stability, in vitro release, cytotoxicity, ocular irritation, mucoadhesion, ocular surface retention, pharmacokinetics, and therapeutic efficacy in a BAC‑induced DED mouse model. Network pharmacology and molecular docking were used to generate testable hypotheses on possible mechanisms of Qu in DED. RESULTS: Qu‑PL‑ISG had a PS of 173.33 ± 1.27 nm, a ZP of -46.87 ± 0.95 mV, and an EE of 88.85 ± 1.41%. It released 46% of Qu over 72 h and remained stable for 21 days at 4 °C, with no cytotoxicity or irritation. Compared with Qu‑PL, Qu‑PL‑ISG exhibited higher mucoadhesive force (3783.5 ± 125.2 vs. 1986.2 ± 145.7 dyne/cm) and longer ocular surface retention (45 vs. 20 min). Ocular bioavailability (AUC‑ ) in cornea, conjunctiva, and tears increased 2.79-, 1.47- and 1.44-fold, respectively. In DED mice, 0.2% Qu‑PL-ISG restored tear secretion, reduced corneal staining, repaired epithelial thickness, increased goblet cell density, and lowered corneal IL-1β and TNF-α levels, with efficacy comparable to 0.05% cyclosporine A. Network pharmacology and molecular docking were used as computational tools to predict that Qu may act on DED through multi‑target interactions (TNF, NF‑κB, STAT3, IL-1β, AKT1, IL-6, Src) and pathways (IL-17, PI3K-Akt, TNF signaling), though these findings require experimental validation. CONCLUSION: Qu‑PL‑ISG is a safe, ion‑activated in situ gel that significantly enhances Qu bioavailability and anti‑inflammatory efficacy, showing promise for DED treatment.
Strontium-Functionalized Biomaterials for Bone Regeneration: Mechanisms, Biological Functions, and Clinical Translational Progress.
Ning F, Wang X, Pan P … +3 more , Liu W, Yan G, Wang X
Int J Nanomedicine · 2026 · PMID 42338898 · Full text
Strontium (Sr), a trace element with osteogenic, anti-resorptive, immunomodulatory, angiogenic, and antibacterial activities, has become an important functional component in biomaterials for bone regeneration. This revie...
Strontium (Sr), a trace element with osteogenic, anti-resorptive, immunomodulatory, angiogenic, and antibacterial activities, has become an important functional component in biomaterials for bone regeneration. This review systematically summarizes Sr-functionalized biomaterials, with emphasis on Sr⁺-mediated molecular mechanisms, concentration-dependent bioactivity, local delivery strategies, fabrication-dependent ion-release behavior, antimicrobial and antioxidant functions, and clinical translational potential. Particular attention is given to the physicochemical regulation of Sr incorporation, therapeutic-ion synergy, fabrication-related release characteristics, and key challenges affecting translational application. In addition, we discuss how Sr cooperates with other therapeutic ions, including Mg, Zn, Cu, Se, and Ga, to coordinate osteogenesis, angiogenesis, immunomodulation, and infection control within the bone-regeneration microenvironment. Current limitations include the lack of unified optimal Sr dosing across different material platforms, insufficient long-term release and biosafety data, limited large-animal and clinical evidence, and an incomplete understanding of Sr-associated antimicrobial mechanisms. Overall, this review provides mechanistic insights and practical guidance for the rational design of next-generation Sr-functionalized bone-repair biomaterials.
Stimuli-Responsive Nanocarriers for Transdermal siRNA Delivery: Mechanisms, Challenges, and Therapeutic Strategies.
Jian Y, Ban M, Yan Z … +6 more , Wang Y, Che Z, Ren W, Cao Y, Wang Z, Yuan Y
Int J Nanomedicine · 2026 · PMID 42338897 · Full text
BACKGROUND: Small interfering RNA (siRNA) holds therapeutic promise for dermatological diseases, but clinical translation is limited by the stratum corneum barrier and the instability of naked siRNA. Nanocarrier-based sy...
BACKGROUND: Small interfering RNA (siRNA) holds therapeutic promise for dermatological diseases, but clinical translation is limited by the stratum corneum barrier and the instability of naked siRNA. Nanocarrier-based systems offer effective solutions by enhancing skin penetration, improving siRNA stability, and enabling targeted intracellular delivery. METHODS: This review synthesizes current evidence on nanocarrier-mediated transdermal siRNA delivery. Key design parameters: particle size, surface charge, degradability, and morphology are evaluated for their roles in skin permeation and intracellular trafficking. Stimuli-responsive nanocarriers (pH, enzymatic, light, temperature) and physical enhancement strategies, including microneedles, sonophoresis, and laser ablation, are also reviewed. RESULTS: Lipid-polymer hybrid nanoparticles demonstrate notable advantages in stability, biocompatibility, and co-delivery capability. Stimuli-responsive systems enable spatiotemporal control of siRNA release, while physical enhancement technologies significantly improve cutaneous permeability. Disease-specific delivery strategies tailored to pathological microenvironments including psoriasis, melanoma, and chronic wounds illustrate the feasibility of adapting material composition, structural parameters, and responsiveness to different therapeutic contexts. CONCLUSION: Advances in intelligent nanomaterials, responsive carrier engineering, and physical facilitation approaches provide a solid foundation for clinically viable transdermal siRNA therapies. Future development will benefit from integrating precise release control with disease-tailored delivery strategies to overcome biological barriers and optimize therapeutic outcomes.
Pulmonary Exposure to Copper Oxide Nanoparticles Induces Systemic Inflammation, Oxidative Stress, and Prothrombotic Responses in BALB/c Mice.
Ferdous Z, Beegam S, Zaaba NE … +3 more , Elzaki O, Greish YE, Nemmar A
Int J Nanomedicine · 2026 · PMID 42333287 · Full text
INTRODUCTION: Copper oxide nanoparticles (CuONPs) are increasingly used in industrial and biomedical applications; however, their potential to provoke systemic vascular and hemostatic disturbances remains poorly defined....
INTRODUCTION: Copper oxide nanoparticles (CuONPs) are increasingly used in industrial and biomedical applications; however, their potential to provoke systemic vascular and hemostatic disturbances remains poorly defined. METHODS: BALB/c mice were subjected to a single pulmonary instillation of CuONPs at doses of 3 µg or 30 µg per mouse, and the endpoints were evaluated 24 h post-exposure. Prior to biological testing, the CuONPs were characterized by X-ray diffraction, dynamic light scattering, zeta potential analyses and transmission electron microscopy, confirming their high crystallinity, relatively uniform particle size distribution and good electrostatic stability. RESULTS: Exposure to CuONPs significantly shortened the thrombotic occlusion times in arterioles and venules; reduced prothrombin and activated partial thromboplastin times; and elevated plasma platelet factor 4, fibrinogen, plasminogen activator inhibitor-1, and C-reactive protein levels, indicating a shift toward a prothrombotic state. Oxidative stress is evidenced by increased levels of thiobarbituric acid-reactive substances, depleted glutathione levels, and decreased nitric oxide levels. In parallel, CuONPs induced significant upregulation of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-6, and IL-1β) and markers of DNA damage and apoptosis, including 8-hydroxy-2'-deoxyguanosine, cytochrome C release, and cleaved caspase-3 expression. DISCUSSION: Collectively, these findings demonstrated that pulmonary exposure to low and high doses of CuONPs triggered systemic oxidative stress and inflammation, leading to prothrombotic responses, DNA damage, and apoptosis. This study highlights the potential vascular risks associated with CuONPs and underscores the importance of careful safety evaluation in biomedical and environmental contexts.
Biomimetic Polymer-Based Nanomaterials for Immune-Responsive Hepatocellular Carcinoma Therapy.
Zhang J, Ma J
Int J Nanomedicine · 2026 · PMID 42333286 · Full text
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths because of its late diagnosis, tumor heterogeneity, compromised liver function, and the poor efficacy of conventional treatment strategies. Altho...
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths because of its late diagnosis, tumor heterogeneity, compromised liver function, and the poor efficacy of conventional treatment strategies. Although immune checkpoint inhibitors and adoptive immune therapy have shown promising results in some patients, these therapies are also less effective overall due to many factors. Biomimetic polymer nanomaterials have recently been explored as novel tools to address these challenges by combining synthetic polymeric carriers with biologically inspired elements, including cell membrane modification, receptor-targeting ligands, and smart designs. This review focuses on the therapeutic potential of the biomimetic polymer-based nanomaterials for hepatocellular carcinoma by covering their liver immunological characteristics, design principles, various types, and immune-modulating mechanisms with preclinical evidence, challenges, limitations, and future perspectives. Studies show that these nanoplatforms enable sustained circulation, evade the immune system, selectively accumulate in tumors, and provide controlled release of immunotherapeutic agents. Biomimetic approaches promote antigen presentation, immune modulation, and immune cell infiltration into the tumor microenvironment. Preclinical evidence shows that nanomaterial-based cancer vaccine therapy, immune cell reprogramming, and combination therapies work in synergy with checkpoint inhibitors to overcome immunosuppression, activate T cells, and suppress tumor growth. Regardless of these promising outcomes, factors such as complexity in fabrication, batch preparation variability, scalability, and biosafety over a long period of time make it difficult to translate them into the clinical environment. There is a need to overcome these challenges by optimal design, standardized preparation, and biosafety evaluation for the clinical translation of biomimetic nanoplatforms.
Gas Vesicles and Acoustic Protein Nanostructures in Molecular Ultrasound Nanomedicine: Translational Archetypes, Biomaterial Design, and Barriers to Clinical Realization.
Cui A, Du Y, Sun L
Int J Nanomedicine · 2026 · PMID 42333285 · Full text
Ultrasound is clinically established, portable, and repeatable, but its dominant contrast logic remains anatomical and perfusion-based. Gas vesicles (GVs), acoustic reporter genes (ARGs), targeted GV derivatives, and GV-...
Ultrasound is clinically established, portable, and repeatable, but its dominant contrast logic remains anatomical and perfusion-based. Gas vesicles (GVs), acoustic reporter genes (ARGs), targeted GV derivatives, and GV-containing release materials have introduced a protein-based route toward molecular ultrasound nanomedicine. Their translation, however, cannot be inferred from acoustic detectability alone. This Review examines GVs and related acoustic protein nanostructures as biomaterial and nanomedicine systems. We distinguish clinical microbubbles, purified GVs, exogenous GV-labeled cells, intracellular ARG systems, GV-based release materials, and prospective computationally designed acoustic protein nanostructures. These formats differ in biological setting, route of administration, pharmacologic burden, and evidentiary maturity. We define computational molecular sonography as a bounded organizing framework that links reporter design, acoustic signal representation, biological fate, exposure estimation, and clinician-governed safety. The strongest current evidence comes from natural and engineered GV systems, including pressure-dependent collapse, nonlinear detection, gas vesicle protein C (GvpC)-mediated surface engineering, blood-component interactions, and reporter-gene imaging. By contrast, fully de novo acoustic protein nanostructures remain prospective rather than in vivo-ready. The major translational barriers include shell mechanics and stability, surface corona and immune clearance, repeat-dose safety, toxicology, manufacturing consistency, critical quality attributes, and Sim-to-Real uncertainty in tissue and acoustic fields. Future clinical value will require standardized biomaterial characterization, direct acoustic phenotyping, reporter-sensitive acquisition, and regulatory-grade control of product and exposure. Ultrasound visibility is therefore necessary but insufficient; translation will depend on aligning material design, biological fate, signal interpretation, and safety as a coupled problem.
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