Journal of Nanobiotechnology最新文献

{"title":"Functionalized metal-organic frameworks as smart nanoplatforms: advancing tumor precision therapy through post-synthetic surface tailoring, challenges, and prospects for clinical translation.","authors":"Shiva Velayati, Masoumeh Zahmatkeshan, Fariba Esmaeili, Seyed Mohammad Hosseini, Seyed Mahdi Rezayat, Mahmoud Reza Jaafari, Kazem Mousavizadeh, Gholamreza Taheripak, Moein Adel, Anna Lesniak, Iraj Alipourfard","doi":"10.1186/s12951-026-04757-9","DOIUrl":"10.1186/s12951-026-04757-9","url":null,"abstract":"<p><p>Metal-organic frameworks (MOFs) have garnered significant attention as versatile nanocarriers for oncological drug delivery, owing to their exceptional porosity, structural tunability, extensive specific surface areas, and favorable drug loading and release kinetics, which collectively enable targeted payload delivery and reduced systemic toxicity. Nevertheless, the clinical promise of unmodified MOFs is severely curtailed by substantial in vivo biological barriers-including rapid bio-clearance, the immunosuppressive and acidic tumor microenvironment (TME), and inefficient cellular internalization-challenges that are ubiquitous across nanomedicine platforms and critically undermine therapeutic outcomes. This review provides a comprehensive examination of post-synthetic modification (PSM) as an indispensable strategy to surmount these obstacles. It systematically categorizes the diverse array of surface modifiers reported to date into natural polymers, synthetic polymers, nonpolymeric small molecules, inorganic materials, and multifunctional hybrid architectures, while elucidating how each class can enhance biocompatibility, colloidal stability, circulation half-life, active targeting, and stimuli-responsive cargo release. Crucially, the review critically appraises the intrinsic trade-offs introduced by surface engineering, including increased hydrodynamic diameter, impaired tumor penetration, heightened synthetic and characterization complexity, and unpredictable perturbations to biodegradation pathways and immune system interactions. Despite robust preclinical validation, the translational trajectory of surface-engineered MOF-based therapeutics remains encumbered by formidable challenges spanning scalable and reproducible manufacturing, long-term biosafety assessment, and stringent regulatory approval. By delineating current advances, critical limitations, and prospective directions, this review highlights the delicate equilibrium between surface functionalization and biological performance that must be achieved to realize the clinical potential of PSM-optimized MOF nanomedicines.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13689023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238802","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":"Schwann cell-derived extracellular vesicles promote periodontal tissue regeneration.","authors":"Ting Zhang, Jiaying Liu, Xiyue Wang, Yu Wu, Mengjia Wang, Shuyu Cheng, Rong Liu, Shuang Zhang, Yangheng Zhang, Yin Xiao, Yanan Zhu, Fuhua Yan","doi":"10.1186/s12951-026-04848-7","DOIUrl":"10.1186/s12951-026-04848-7","url":null,"abstract":"<p><p>Periodontitis is a common chronic inflammatory disease worldwide, and conventional therapies control inflammation but fail to achieve predictable regeneration. The inferior alveolar nerve (IAN) is a key peripheral nerve that governs mandibular bone homeostasis, and its disruption precipitates bone metabolic imbalance and impaired repair. However, the dynamic behavior of Schwann cells (SCs), the principal glial cells of this neural axis, and their mechanistic influence on periodontal ligament stem cells (PDLSCs) remain elusive. We established a rat IAN transection model and found that denervation induced progressive alveolar bone deterioration and compromised the osteogenic capacity of resident PDLSCs. Correlation analyses revealed that this bone deterioration coincided with progressive SC depletion in periodontal tissue, suggesting a link between Schwann cell loss and PDLSC dysfunction. Transcriptomic profiling of denervated PDLSCs revealed that dysregulated AMPK/mTOR signaling and suppressed autophagy are mechanisms underlying osteogenic impairment. Co-culture with SCs restored PDLSC proliferation and osteogenic differentiation, with SC-derived extracellular vesicles (SC-EVs) as important paracrine mediators of this effect. Mechanistically, SC-EVs delivered rno-miR-210-5p, which targeted the DAP1 gene and suppressed its expression, thereby activating the AMPK/mTOR-autophagy axis and rescuing osteogenic potential. In a rat denervated mandibular defect model, SC-EVs significantly enhanced bone regeneration. Collectively, these findings suggest that Schwann cells and their EVs participate in the neural regulation of periodontal bone metabolism and may play an important role in periodontal regeneration.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238799","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":"Plant-derived extracellular vesicles deliver spermidine to reprogram macrophage metabolism and ameliorate rheumatoid arthritis.","authors":"Xiaocheng Wang, Jiaxin He, Yixiang Hong, Xingyue Zeng, Min Li, Shixiong Cao, Renge Liang, Gengmin Zhou, Qingwen Wang","doi":"10.1186/s12951-026-04836-x","DOIUrl":"10.1186/s12951-026-04836-x","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is driven by macrophage-mediated synovial inflammation closely linked to metabolic dysfunction, highlighting immunometabolism as a therapeutic target. Here, we engineered spermidine-loaded red cabbage-derived extracellular vesicles (RCEVs@SPD) as a plant-based nanoplatform to reprogram macrophage bioenergetics. In LPS-stimulated macrophages, RCEVs@SPD suppressed pro-inflammatory polarization and enhanced mitochondrial function, as evidenced by increased ATP production and mitochondrial membrane potential. Assay-based measurements further showed reduced extracellular acidification rate (ECAR) and elevated oxygen consumption rate (OCR), indicating a shift from glycolysis toward oxidative phosphorylation (OXPHOS). Untargeted LC-MS metabolomics revealed coordinated alterations in pathways supporting mitochondrial cofactor biosynthesis, redox balance, and central carbon metabolism. Transcriptomic analysis confirmed enrichment of OXPHOS and mitochondrial respiration gene signatures with concomitant repression of glycolytic programs and PI3K-AKT signaling. In vivo, RCEVs@SPD significantly alleviated collagen-induced arthritis, improved joint histopathology, and promoted anti‑inflammatory macrophage polarization. Notably, systemic macrophage depletion abolished the additional therapeutic benefit of RCEVs@SPD, demonstrating macrophage dependence. Collectively, these findings establish plant-derived extracellular vesicles as a biocompatible delivery system that potentiates spermidine to restore macrophage metabolic balance and mitigate RA pathology.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238782","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":"Lactobacillus mucosae extracellular vesicles improve metabolic dysfunction-associated fatty liver disease by activating the AMPK pathway via the gut-liver axis.","authors":"Kaige Zhang, Yuyu Zeng, Zhaohui Liao, Jianhua Wu, Xilong Zhang, Tingtao Chen, Zhengyuan Xie","doi":"10.1186/s12951-026-04843-y","DOIUrl":"10.1186/s12951-026-04843-y","url":null,"abstract":"<p><strong>Background and objective: </strong>Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver disease worldwide but lacks effective therapies. Gut microbiota play a key role in MAFLD via the gut-liver axis, yet targeted interventions remain unclear. This study investigates the therapeutic effects and mechanisms of Lactobacillus mucosae (L. mucosae) and its extracellular vesicles (EVs) in MAFLD.</p><p><strong>Methods: </strong>At the clinical level, 16S rRNA sequencing was performed to analyze differences in gut microbiota composition between MAFLD patients and healthy controls, followed by the identification of a core probiotic strain, L. mucosae, using culture-based approaches. A high-fat diet-induced MAFLD mouse model was subsequently established to evaluate the therapeutic effects of L. mucosae, while free fatty acid-induced hepatocyte models were used to identify L. mucosae-EVs as the key active component. Mechanistic investigations and validation were further conducted in vivo and in vitro using RNA sequencing, qPCR, Western blot analyses, DIA-based EV proteomics, and Proteinase K-mediated EV protein functional assays.</p><p><strong>Results: </strong>MAFLD patients showed reduced intestinal Lactobacillus abundance, negatively correlated with hepatic lipid parameters. L. mucosae administration alleviated steatosis, metabolic dysfunction, inflammation, and oxidative stress in mice. In vitro, L. mucosae-EVs were confirmed as the main active component, and Proteinase K-pretreated EVs showed attenuated protective effects on hepatocytes. Mechanistically, L. mucosae-EVs activated hepatic AMPK signaling via the gut-liver axis, remodeled gut microbiota, and restored intestinal barrier integrity.</p><p><strong>Conclusion: </strong>This study systematically demonstrates for the first time that L. mucosae-EVs ameliorate MAFLD through multiple mechanisms, including gut microbiota remodeling, intestinal barrier restoration, and activation of hepatic AMPK signaling via the gut-liver axis. Proteinase K-mediated functional assays suggest that EV-associated protein cargo contributes, at least in part, to these protective effects. These findings provide a solid experimental foundation and theoretical basis for the development of precision microbiome-based therapeutic strategies for MAFLD based on L. mucosae and its EVs.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13689356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238726","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 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}