Journal of Nanobiotechnology最新文献

{"title":"A programmable nanoplatform for inflammatory-state reprogramming in psoriasis treatment.","authors":"Zhihua Chen, Jinyu Zhao, Shiqi Huang, Ge Lou, Mingji Jin, Zheng Nan, Zhonggao Gao, Shuangqing Wang, Jingchun Jin","doi":"10.1186/s12951-026-04842-z","DOIUrl":"10.1186/s12951-026-04842-z","url":null,"abstract":"<p><p>Psoriasis is a chronic, immune-mediated inflammatory skin disease. Although current treatments alleviate symptoms, they primarily focus on inflammation suppression through single-target approaches, which fail to comprehensively address the complex pathological imbalances. To overcome this limitation, we developed a programmable delivery system based on a nanocomposite material composed of Tannic acid (TA), Cerium (Ce), and Luteolin (Lut), integrated into an in situ gelling hydrogel platform (TA-Ce-Lut-Gel), enabling multi-dimensional treatment strategy for psoriasis by precisely modulating oxidative stress, immune responses, and skin microbiota. The TA-Ce-Lut metal-polyphenol nanoparticles, constructed through coordination bonds, exhibited a size of 177.30 ± 0.55 nm and high encapsulation efficiency of 72.89 ± 5.32%. Upon incorporation into the hydrogel, this system provided a localized and sustained drug depot. In an imiquimod-induced mouse model of psoriasis (both ear and back), TA-Ce-Lut-Gel significantly reduced skin inflammation, improved skin thickness, erythema, and scaling, showing superior efficacy compared to traditional anti-inflammatory treatments. This system alleviated ROS levels, regulated macrophage M2 polarization, and reshaped the immune response, while also modulating the TRAF6/NF-κB/STAT3 signaling pathway to significantly inhibit pro-inflammatory cytokine secretion. Additionally, combined with NIR irradiation, TA-Ce-Lut-Gel enhanced transdermal drug delivery and antioxidant activity, further enhancing therapeutic effects and promoting skin microbiota recovery. This study presents an effective platform for localized precise treatment of psoriasis, overcoming the limitations of traditional single-target anti-inflammatory therapies and offering a potential strategy for the treatment of other immune-mediated diseases, with broad clinical application prospects.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI-guided design and biomaterial integration for next-generation extracellular vesicle therapeutics: an evidence-weighted translational framework.","authors":"Jiaqi Tian, Qiang Li, Ning Li, Dandan Song, Zengfeng Li, Xiaotan Shi, Huiyu Sun, Shuyin Duan, Lin Zhang","doi":"10.1186/s12951-026-04831-2","DOIUrl":"10.1186/s12951-026-04831-2","url":null,"abstract":"<p><strong>Abractst: </strong>Extracellular vesicles (EVs) are promising therapeutic and diagnostic platforms, yet their clinical translation remains constrained by population heterogeneity, limited target-site retention, uncertain biodistribution, and variable potency. These persistent limitations have motivated the convergence of artificial intelligence (AI), biomaterials, synthetic biology, and advanced validation systems into what we describe as a next-generation EV framework. The evidence supporting these enabling technologies is, however, uneven. AI methods have demonstrated clear value for retrospective classification and feature discovery but have rarely been prospectively validated for therapeutic design; biomaterial carriers provide measurable gains in local retention and release control yet show inconsistent reporting of EV integrity, dose normalization, and controls; and programmable or trigger-responsive EV systems remain largely preclinical. A similar pattern is evident in the clinical landscape, where trial activity in EV-based interventions continues to grow but most studies remain in early or exploratory phases and no FDA-approved EV therapy is currently available. We therefore present next-generation EVs as an evidence-weighted translational agenda with future progress contingent on validated potency assays, reproducible manufacturing, predictable biodistribution, and a clear separation of demonstrated systems from longer-term concepts.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of the miR-210-3p-EFNA3-YAP axis and its targeted modulation via biomimetic supramolecular nanoparticles to promote ischemic flap survival.","authors":"Jie Xu, Xiuxiu Zhuang, Zichang Wu, Fuyi Yan, Deen Shi, Fan Ye, Ruihua Ding, Qi Gao, Qimin Yao, Yiying Liu, Xiaoyu Dong, Fan Zhang, Binbiao Li, Xiangwei Xu, Hongfei Tong, Yanzhi Yao, Wenbing Jiang, Jian Xiao, Zhenglin Li, Wei Chen","doi":"10.1186/s12951-026-04833-0","DOIUrl":"10.1186/s12951-026-04833-0","url":null,"abstract":"<p><p>Ischemic skin flaps are highly susceptible to distal necrosis because of insufficient perfusion, oxidative stress, and dysregulated cell death. Here, we investigated the role of Hippo/YAP signaling in ischemic flap survival and identified its upstream regulatory mechanism. Hippo pathway inactivation, characterized by reduced MST1/2 and LATS1/2 phosphorylation and enhanced YAP nuclear localization, was preferentially associated with viable flap regions. Mechanistically, ischemia-induced HIF-1α upregulated miR-210-3p, which suppressed ephrin-A3 (EFNA3), weakened the EFNA3-YAP interaction, and promoted YAP nuclear translocation. Re-expression of EFNA3 partially reversed miR-210-3p-induced YAP activation and cytoprotection, confirming its functional involvement. Mechanistically, ischemia-induced HIF-1α increased miR-210-3p expression, which suppressed EFNA3 and facilitated YAP nuclear localization. EFNA3 re-expression partially reversed miR-210-3p-induced YAP activation, supporting its functional involvement. MiR-210-3p treatment was further associated with reduced oxidative injury, lipid peroxidation, mitochondrial dysfunction, and ferroptosis-related molecular alterations, together with improved perfusion and flap survival. In vivo, miR-210-3p improved local perfusion and flap survival. We further developed a virus-inspired biomimetic nanoparticle for miR-210-3p delivery, which achieved protective effects comparable to AAV-mediated delivery in vitro and in vivo. These findings identify the miR-210-3p-EFNA3-YAP axis as an important regulator of ischemic tissue adaptation and provide a non-viral miRNA delivery strategy for ischemic flap repair.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13689359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel inhalable tanshinone IIA lipid nanocrystal formulation for the enhanced treatment of idiopathic pulmonary fibrosis.","authors":"Qin Wang, Yun Zhao, Yuanhu Mao, Xiaobo Zhang, Lei Huang, Lei Tang, Yi Chen, Zipeng Gong, Jianqing Peng","doi":"10.1186/s12951-026-04786-4","DOIUrl":"10.1186/s12951-026-04786-4","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease marked by relentless deterioration of pulmonary function. Clinically, oral pharmacotherapy for IPF is hampered by two major limitations: inefficient drug delivery to the lung parenchyma and systemic exposure leading to unavoidable off-target side effects. In this study, we developed an inhalable tanshinone IIA (TA) formulation based on lipid nanocrystals to address these challenges. Leveraging the high drug loading capacity and structural stability of lipid nanocrystals, this platform overcomes the intrinsic hydrophobicity of TA, thereby markedly improving its aqueous dispersibility, aerosolization performance, and regional deposition in the deep lung. In vitro, TA lipid nanocrystals significantly enhanced cellular uptake in both pulmonary epithelial cells and lung fibroblasts. In vivo, they achieved substantially high and sustained pulmonary drug exposure. In a bleomycin-induced mouse model of IPF, inhaled TA lipid nanocrystals attenuated histopathological fibrosis, preserved lung function, and suppressed chronic inflammation via modulating the PI3K-Akt signaling pathway and the coagulation-fibrinolysis system. Collectively, this study establishes TA as a promising inhaled therapeutic agent for IPF and introduces lipid nanocrystals as a versatile, scalable, and clinically translatable platform for targeted pulmonary delivery in fibrotic and other chronic respiratory diseases.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-cascade oxygen-generating hydrogel/nanofibrous membrane composites restore periodontal microenvironment homeostasis.","authors":"Ye Liang, Fan Yang, Jun Kang, Zijun Chen, Ting Zou, Shaohua Ge, Chengfei Zhang","doi":"10.1186/s12951-026-04835-y","DOIUrl":"10.1186/s12951-026-04835-y","url":null,"abstract":"<p><p>The hypoxic environment of deep periodontal pockets favors the thriving of anaerobic microbes, leading to dysbiosis, tissue destruction, and treatment resistance. Elevating intra-pocket oxygen tension is a fundamental yet unmet need for controlling anaerobic pathogens in deep periodontal pockets. Our previous study demonstrated the therapeutic efficacy of oxygen-releasing hydrogel based on calcium peroxide (CPO) in reducing anaerobic pathogens in vitro. However, the rapid hydrolysis of unprotected CPO in an aqueous system and the potential oxidative damage induced by the intermediate hydrogen peroxide (H₂O₂) limit its clinical applicability. To address these issues, we developed a dual-layer, self-cascade oxygen-generating composite (PCA-GC) to sustain topical oxygen enrichment in deep periodontal pockets. The inner layer consists of a hydrophobic polycaprolactone (PCL) nanofibrous membrane encapsulating CPO (designated PCA) to achieve long-term stability and controlled hydrolysis. Surrounding this core, a flexible gelatin methacryloyl-cerium oxide hydrogel (GC) served as a protective outer layer to decompose self-generated H₂O₂ via its catalase-like activity, thereby preventing H₂O₂ accumulation and shielding adjacent tissues. Our results showed that PCA-GC sustained oxygen release for up to 5 days, demonstrating satisfactory biocompatibility with human gingival fibroblasts and periodontal ligament cells. Furthermore, PCA-GC significantly alleviated hypoxia in multispecies biofilms and effectively eradicated periodontal pathogens, including Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum). In multispecies biofilms, the proportion of P. gingivalis decreased significantly from 84.42% to 0.05%, while the commensal Streptococcus gordonii increased from 11.18% to 99.01%, reflecting a shift from a pathogen-dominated to a commensal-dominated microbial community. Additionally, PCA-GC enhanced pathogen-clearance function in macrophages under hypoxia by increasing reactive oxygen species and nitric oxide production. In rat experimental periodontitis models, PCA-GC decreased hypoxia marker expression, reduced pathogen burden and alveolar bone loss, suppressed osteoclast activity, and attenuated inflammatory response. Collectively, sustained oxygen therapy via PCA-GC effectively remodels the periodontal microenvironment, suppresses pathogenic dysbiosis, and enhances host antimicrobial responses, underscoring its potential as an adjunctive strategy for treating periodontitis.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HAMA microneedles patch loaded with muscle-targeting engineered apoptotic vesicles and attenuating sarcopenia by regulating mitochondrial homeostasis.","authors":"Jiayao Zhang, Zhao Lin, Haiqi Ding, Mingjuan Zhang, Yibin Su, Linhai Yang, Dingqiang Chen, Xuanhao Chen, Jun Luo, Fuli Wen, Guoyu Yu, Zineng Yan, Jie Xu","doi":"10.1186/s12951-026-04813-4","DOIUrl":"10.1186/s12951-026-04813-4","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia is an age-related disorder characterized by the progressive loss of skeletal muscle mass and function, primarily driven by mitochondrial dysfunction, oxidative stress, and impaired satellite cell activity. Conventional therapeutic strategies have shown limited efficacy in restoring muscle performance. Apoptotic vesicles (ApoVs) derived from mesenchymal stem cells (MSCs) have recently emerged as promising therapeutic agents capable of delivering bioactive cargos to regulate cellular metabolism and attenuate tissue aging. However, the targeted delivery and functional stability of ApoVs remain major challenges.</p><p><strong>Results: </strong>We engineered human umbilical cord MSC-derived ApoVs with the muscle-specific aptamer A01B and encapsulated them in a methacrylated hyaluronic acid (HAMA) hydrogel microneedle patch to enhance tissue targeting and enable sustained release. In vitro, ApoVs were efficiently internalized by C2C12 myotubes and alleviated dexamethasone-induced atrophy by promoting proliferation, reducing oxidative stress, restoring mitochondrial structure and function, and modulating the PTEN-PI3K-AKT signaling pathway. miRNA profiling identified miR-21-5p as a key ApoV-delivered effector that activates this pathway. In vivo, treatment with the aptamer-functionalized ApoV microneedle system significantly improved muscle mass, myofiber cross-sectional area, mitochondrial oxidative capacity, and functional endurance in sarcopenic mice compared with controls.</p><p><strong>Conclusions: </strong>Our findings demonstrate that the muscle-targeted delivery of engineered ApoVs via HAMA microneedles effectively reverses key hallmarks of sarcopenia by restoring mitochondrial homeostasis and activating PI3K/AKT signaling through miR-21-5p. This microneedle-based ApoV platform provides a promising cell-free therapeutic strategy for ameliorating muscle atrophy and functional decline.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Composite antibiotic-loaded nano-platelet vesicle and mineralized hydrogel system for the treatment of infected bone defects.","authors":"Zhanqiu Dai, Zijie Wang, Yongcheng Wang, Jiahao Zhu, Ke Yang, Sheng Cheng, Chenghao Wu, Qing Qiu, Weiyang Gao, Pengfei Chen","doi":"10.1186/s12951-026-04799-z","DOIUrl":"10.1186/s12951-026-04799-z","url":null,"abstract":"<p><p>Complex bone infections are challenging to treat clinically because of their high incidence, recalcitrance, and tendency to recur, with Staphylococcus aureus (S. aureus) being the predominant pathogen. The infection microenvironment disrupts the osteoclast-osteoblast balance, leading to progressive bone loss and posing a major therapeutic challenge. Conventional treatment strategies limited to antibiotics or bone grafts often fail because of issues such as biofilm persistence or a lack of osteoinductive activity. Therefore, highly effective and precise treatment strategies for infected bone defects are urgently needed. In this study, an integrated system combining gentamicin-loaded nano-platelet vesicles (NPVs) with a calcium phosphate (CaP)-mineralized hydrogel was developed. The NPVs serve as effective antibiotic carriers to aid in the elimination of bacteria and reduction in bacterial-induced osteoclast overactivation. Furthermore, the CaP component in the mineralized hydrogel significantly promoted the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Transcriptomic analysis and experimental validation confirmed that the composite hydrogel promoted osteogenic differentiation of BMSCs through activation of the Wnt/β-catenin signalling pathway. Together, this composite platform provides efficient antibacterial activity, suppresses excessive osteoclast activation, and promotes osteogenic differentiation, as validated in an infected bone defect model. Through multimodal synergy, the system enables effective drug delivery, reliable infection control, and bone microenvironment modulation, offering a comprehensive therapeutic strategy for bone infections.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13711879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149268982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A self-sufficient nanoreactor orchestrating calcium overload and sonodynamic/chemodynamic-amplified ferroptosis for oral squamous cell carcinoma therapy.","authors":"Lei Wu, Chuiyin Wang, Qian Chen, Aiqi Wang, Meiying Peng, Gengming Zhang, Mingxin Cao, Zhaoyang Guo, Xiaoying Yang, Yinsong Wang","doi":"10.1186/s12951-026-04783-7","DOIUrl":"10.1186/s12951-026-04783-7","url":null,"abstract":"<p><p>Bacteria-derived components hold great promise for cancer therapy owing to their versatile biological properties. We previously reported that Porphyromonas gingivalis cell walls (PgCW), rich in intrinsic µ-oxo bisheme ([Fe(III)PPIX]₂O), can effectively mediate both sonodynamic therapy (SDT) and chemodynamic therapy (CDT). More recently, we identified PgCW's inherent potential to trigger ferroptosis. However, its therapeutic efficacy is limited by the hypoxic tumor microenvironment (TME) and insufficient endogenous hydrogen peroxide (H₂O₂) required for catalytic reactions. Herein, a self-sufficient nanoreactor (DCP) was developed by depositing calcium peroxide (CaO₂) within dendritic large-pore mesoporous silica nanoparticles (DLMSNs), followed by the electrostatic adsorption of PgCW. Under ultrasound irradiation, DCP combines SDT and CDT with continuous glutathione (GSH) depletion to trigger ferroptosis. In the acidic TME, the decomposition of CaO₂ generates O₂ to enhance PgCW-mediated SDT, supplies H₂O₂ for Fenton-like CDT, and releases Ca²⁺ to induce calcium overload. The abundant reactive oxygen species (ROS) from CaO₂-supplemented SDT and CDT, together with GSH exhaustion, amplify ferroptosis, driving severe lipid peroxidation (LPO) and cell membrane rupture to release damage-associated molecular patterns (DAMPs) for primary tumor regression. Furthermore, intracellular calcium overload synergistically promotes this ferroptosis-mediated immunogenic cell death (ICD), which, combined with the innate adjuvanticity of PgCW, drives robust systemic immune activation to suppress distant tumors. In summary, this nanoreactor overcomes TME limitations through self-sufficient substrate supply and efficiently combines calcium overload with amplified ferroptosis to suppress the growth and metastasis of oral squamous cell carcinoma (OSCC). These findings suggest a potential strategy for precision cancer immunotherapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucus and tumor penetrating paclitaxel micelles for potent local therapy of cervical cancer.","authors":"Yijie Chen, Yangla Xie, Jiaping Wu, Xianguo Qu, Youqing Shen, Nasha Qiu, Zhifen Zhang","doi":"10.1186/s12951-026-04528-6","DOIUrl":"10.1186/s12951-026-04528-6","url":null,"abstract":"<p><p>The therapeutic efficacy for cervical cancer treatment is limited by insufficient drug accumulation and penetration due to physiological barriers such as mucin-rich environments after systemic administration. Thus, developing a local drug delivery system is essential to overcome these hindrances. Active transcytosis of cancer nanomedicines holds great promise for enhancing tumor extravasation, infiltration, and antitumor activity. Herein, polyzwitterionic OPDEA-PCL was developed to encapsulate paclitaxel (PTX) into micelles, serving as an intravaginal therapy for orthotopic cervical cancer. The OPDEA-PCL/PTX micelles efficiently penetrated mucus and exhibited strong resistance to mucin fouling, thereby facilitating rapid transcytosis into tumors. Furthermore, OPDEA-PCL/PTX micelles colocalized with the mitochondria of tumor cells, reversing PTX resistance. In the orthotopic cervical tumor model, the inhibition rate of OPDEA-PCL/PTX micelles was 90.0%, more than 2-fold higher than that of free PTX. In the subcutaneous cervical cancer model which is resistant to PTX. Intravenous administration of OPDEA-PCL/PTX micelles significantly overcame PTX resistance, achieving a tumor inhibition rate of 95.2%, and extending the median survival time by more than 2-fold compared to free PTX and PEG-PCL/PTX treated groups. In summary, this approach holds great promise as a potent localized nanomedicine for cervical cancer treatment with minimal side effects.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reprogramming microglia via ShK-modified extracellular vesicles promotes immunomodulation and functional recovery after spinal cord injury.","authors":"Zuomeng Wu, Yunxiao Fang, Yue Qin, Yixiang Dong, Cancan Wang, Ruocheng Guo, Qi Sha, Ao Liu, Chongyu Jia, Tianyu Han, Peiwen Song, Cailiang Shen","doi":"10.1186/s12951-026-04822-3","DOIUrl":"10.1186/s12951-026-04822-3","url":null,"abstract":"<p><p>Microglia play a dual role in tissue repair and inflammatory responses following spinal cord injury (SCI), rendering the regulation of their immune activity a key therapeutic objective during disease progression. Single‑cell RNA sequencing revealed a significant upregulation of Kv1.3 expression in microglia following SCI, implicating this channel in the initiation of early neuroinflammation. To selectively target Kv1.3, engineered extracellular vesicles displaying ShK (ShK-EVs), a highly selective Kv1.3‑blocking peptide, were developed. These ShK‑EVs efficiently accumulated at the lesion site and were preferentially internalized by activated microglia. Integrated high‑throughput miRNA sequencing and proteomic profiling indicated that ShK‑EVs possess substantial neurorepair potential. Mechanistically, ShK‑EVs suppressed M1‑type microglial polarization and reduced the secretion of pro‑inflammatory cytokines by modulating the JAK/STAT signaling pathway. This modulation resulted in reduced tissue cavitation and neuronal apoptosis, enhanced neuronal survival and axonal regeneration, and ultimately led to a significant improvement in motor function in SCI mice. Taken together, these findings identify Kv1.3 as a key regulator of microglial activation after SCI and provide a novel, targeted therapeutic strategy using ShK‑EVs, offering new perspectives on immunomodulation of the injury microenvironment and functional neural recovery.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}