Lingling Zhou, Jiayuan Sun, Tianxiang Lu, Xinya Zhang, Mingkang Wang, Yanjun Xu, Jia Zhou, Xiaoyang Li, Wenxian Du, Fan Yang, Yuehua Li
{"title":"Electron-injected Pd@CeO<sub>2</sub> nanozymes for multifaceted ROS scavenging and protection against ischemia-reperfusion injury in skin flaps.","authors":"Lingling Zhou, Jiayuan Sun, Tianxiang Lu, Xinya Zhang, Mingkang Wang, Yanjun Xu, Jia Zhou, Xiaoyang Li, Wenxian Du, Fan Yang, Yuehua Li","doi":"10.1186/s12951-025-03775-3","DOIUrl":"https://doi.org/10.1186/s12951-025-03775-3","url":null,"abstract":"<p><p>Ischemia-reperfusion (I/R) injury in skin flap transplantation causes acute oxidative damage and inflammation, leading to high failure rates and tissue necrosis. Herein, we present a core-shell Pd@CeO<sub>2</sub> nanozymes that addresses this challenge via a unique electron-injection mechanism across the Pd-CeO<sub>2</sub> interface, conferring unprecedented antioxidant and anti-inflammatory potency. Constructed by confining Pd clusters within a ceria matrix, this nanozyme combines catalase- and superoxide dismutase-like catalytic activities for robust reactive oxygen species (ROS) scavenging. In vitro, Pd@CeO<sub>2</sub> rapidly neutralizes ROS, preventing oxidative cell death by reducing apoptosis and dampening inflammatory signaling, while restoring angiogenic potential. In a rat skin flap I/R model, Pd@CeO<sub>2</sub> significantly improves flap survival and microvascular regeneration while concurrently reducing tissue necrosis, apoptosis, and inflammation, with no observable toxicity. By simultaneously alleviating oxidative stress, cell death, inflammation, and vascular dysfunction, this nanozyme offers a comprehensive therapeutic strategy against I/R injury. This work introduces a new paradigm for nanozyme-based cytoprotection in transplantation, with potential applicability to other ischemic injuries.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"686"},"PeriodicalIF":12.6,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fe-doped phase-transition nanodroplets for synergistic photothermal and starvation-enhanced ferroptosis in cancer therapy.","authors":"Yuhang Tian, Xiang He, Yanchi Yuan, Chunyue Wang, Mengchi Zhang, Hui Jiang, Huajing Yang, Kuikun Yang, Hui Jing","doi":"10.1186/s12951-025-03726-y","DOIUrl":"10.1186/s12951-025-03726-y","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis therapy has emerged as a promising antitumor strategy by utilizing the Fenton reaction to destroy cancer cells, where Fe<sup>2+</sup> catalyzes the decomposition of H<sub>2</sub>O<sub>2</sub> into hydroxyl radicals (•OH). Despite the great potential of ferroptosis therapy in suppressing tumor growth, inadequate catalysts and reactants within tumors remains a major challenge before its clinical translation. Herein, we developed glucose oxidase (GOx)-loaded phase-transition nanodroplets (PND) modified with Fe-tannic acid (TA) networks (PND@GOx@Fe-TA) for enhanced antitumor efficacy of ferroptosis therapy via synergistic photothermal and starvation therapy.</p><p><strong>Results: </strong>PND@GOx@Fe-TA can convert glucose into H<sub>2</sub>O<sub>2</sub>, which not only provides sufficient H<sub>2</sub>O<sub>2</sub> for Fenton reaction, but also consumes glucose to exert starvation therapy. In addition, the Fe-TA networks of PND@GOx@Fe-TA can be degraded upon reaching the tumor site, thus generating Fe<sup>2+</sup> from Fe<sup>3+</sup> via reduction by the overexpressed glutathione (GSH) in the tumor microenvironment. The Fe<sup>2+</sup> then reacts with the in situ-generated H<sub>2</sub>O<sub>2</sub> for enhanced Fenton reaction and induces ferroptosis of cancer cells. Additionally, the PND@GOx@Fe-TA exhibits photothermal effects under 808 nm laser irradiation, which not only accelerates the Fe<sup>2+</sup>-mediated Fenton reaction but also gasifies the liquid core of the PND, enabling its use as a contrast agent for contrast-enhanced ultrasound (CEUS), photoacoustic imaging (PAI) and magnetic resonance imaging (MRI).</p><p><strong>Conclusions: </strong>In summary, the PND@GOx@Fe-TA represents a promising approach for multimodal imaging-guided antitumor therapy by synergistic starvation, photothermal and enhanced ferroptosis therapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"684"},"PeriodicalIF":12.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12533436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308247","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}
Hongshuo Shi, Boxian Pang, Fenglei Zhang, Zhijiang Guo, Wenshi Xu, Man Zheng, Yang You, Guobin Liu, Yifeng Nie, Jianxiao Liang, Xing Chang
{"title":"A novel ligustrazine-based nanodelivery system protects against doxorubicin-induced cardiotoxicity by targeting the SIRT5-DUSP1 axis for mitochondrial repair.","authors":"Hongshuo Shi, Boxian Pang, Fenglei Zhang, Zhijiang Guo, Wenshi Xu, Man Zheng, Yang You, Guobin Liu, Yifeng Nie, Jianxiao Liang, Xing Chang","doi":"10.1186/s12951-025-03667-6","DOIUrl":"10.1186/s12951-025-03667-6","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX)-induced cardiotoxicity (DIC) injury primarily contributes to anthracycline-associated end-stage cardiovascular mortality. Ligustrazine (LIG), a natural compound extracted from Ligusticum chuanxiong, a medicinal plant, has cardioprotective effects. However, therapeutic applications of LIG are limited owing to its poor water solubility, rapid degradation, and low bioavailability. These limitations can be overcome by encapsulating LIG into nanocarriers. We highlight the therapeutic potential of LIG drug delivery technology (LIG-Na) for DIC by integrating bioinformatics, single-cell sequencing, spatial transcriptomics, and transgenic animal models, and investigate the mechanisms underlying mitochondrial homeostasis (MQH).</p><p><strong>Methods: </strong>We used bioinformatics to predict DIC-related mechanisms and established DOX-induced models using SIRT5/DUSP1/PHB2<sup>CKO</sup> mice and DUSP1 transgenic mice (SIRT5/DUSP1/PHB2<sup>TG</sup>). The pathological mechanisms of LIG-Na-mediated alleviation of cardiac injury were examined using echocardiography, WB, TEM, and fluorescence staining. In addition, mitochondrial functional and morphological changes were evaluated using qPCR, ELISA, and confocal laser scanning microscopy following si/adRNA-mediated silencing of SIRT5/DUSP1/PHB2 in cardiomyocytes to further assess the targeted therapeutic effects of LIG-Na.</p><p><strong>Results: </strong>DOX treatment induced severe mitochondrial dysfunction, which was effectively normalized by LIG-Na. Although these protective effects were completely abolished in SIRT5/DUSP1/PHB2<sup>CKO</sup> mice, these remained unaffected in SIRT5/DUSP1/PHB2<sup>TG</sup> mice.</p><p><strong>Conclusion: </strong>LIG-Na ameliorated DOX-mediated cardiac dysfunction and MQH dysregulation through the SIRT5/DUSP1-PHB2S91 phosphorylation axis, thereby effectively suppressing mitochondrial dysfunction and mitigating DIC in mice.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"681"},"PeriodicalIF":12.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292465","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}
Jingru Han, Yinyin Huang, Yadong Guo, Yongshan Li, Jiang Chen, Janak Lal Pathak, Liping Wang, Lan Yang
{"title":"Mesenchymal stem cell-derived apoptotic vesicles: emerging cell-free strategy for periodontitis treatment.","authors":"Jingru Han, Yinyin Huang, Yadong Guo, Yongshan Li, Jiang Chen, Janak Lal Pathak, Liping Wang, Lan Yang","doi":"10.1186/s12951-025-03649-8","DOIUrl":"10.1186/s12951-025-03649-8","url":null,"abstract":"<p><p>Periodontitis is a chronic infectious disease characterized by the destruction of periodontal supporting tissues. Traditional treatment methods, including scaling and root planing, have limited effectiveness in restoring damaged periodontal tissues, necessitating the exploration of new periodontitis treatment strategies. Recently, the transplantation of mesenchymal stem cells (MSCs) has made some progress in periodontitis treatment. However, scholars have found that exogenous MSCs undergo substantial apoptosis shortly after transplantation, complicating the understanding of MSCs' specific mechanisms of action in periodontitis treatment. Notably, recent studies have reported that cells post-apoptosis can exert therapeutic effects through apoptotic vesicles (ApoVs). Several studies have confirmed that ApoVs derived from MSCs (MSC-ApoVs) have potential therapeutic effects in various disease models through immunomodulation, inflammation suppression, tissue regeneration, and drug delivery. Considering that immunomodulation, inflammatory response, and tissue regeneration are core objectives of periodontitis treatment, MSC-ApoVs show broad application prospects. This review discusses the research progress and application potential of MSC-ApoVs in the field of periodontitis treatment and compares their significant advantages over traditional stem cell transplantation techniques. This review also deepens our understanding of the mechanisms of action of MSC-ApoVs and guides us in their future clinical applications in periodontitis treatment.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"679"},"PeriodicalIF":12.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292439","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}
Chen-Guang Zhang, Chen-Yun Yeh, Sheng-Yun Hsu, Mridula Prakash, Adrian B Abarientos, Hsi-Ming Chiang-Hsieh, You-Yu Lin, Christopher Llynard D Ortiz, Lee-Wei Yang, Pi-Hui Liang, Han-Chung Wu, Yungling Leo Lee
{"title":"Dendritic cell-targeted liposomes for cancer immunotherapy via inhibition of aryl hydrocarbon receptor.","authors":"Chen-Guang Zhang, Chen-Yun Yeh, Sheng-Yun Hsu, Mridula Prakash, Adrian B Abarientos, Hsi-Ming Chiang-Hsieh, You-Yu Lin, Christopher Llynard D Ortiz, Lee-Wei Yang, Pi-Hui Liang, Han-Chung Wu, Yungling Leo Lee","doi":"10.1186/s12951-025-03756-6","DOIUrl":"10.1186/s12951-025-03756-6","url":null,"abstract":"<p><p>Ligands for the aryl hydrocarbon receptor (AhR), such as kynurenine derived from the tumor microenvironment, are well-known immunosuppressants. Although systemic AhR inhibition has demonstrated antitumor activity in previous studies, the specific effects of targeting AhR in dendritic cells (DCs) remain unclear. Here, we identified a CD11c-targeting peptide (SP65) with high specificity for DCs using phage display. SP65-functionalized liposomes showed enhanced drug uptake and selectivity for DCs both in vitro and in vivo. Incorporating the AhR inhibitor CH223191, we developed SP65-lipo-CH, which promoted IL-12 secretion in DCs. When co-cultured with SP65-lipo-CH-pretreated DCs, natural killer (NK) cells exhibited increased IFN-γ production and tumor-killing activity. In MC38 and metastatic LLC mouse models, SP65-lipo-CH alone suppressed tumor growth and prolonged survival. These findings suggest that SP65-lipo-CH effectively targets DCs to modulate innate immunity, representing a promising strategy for cancer immunotherapy. Through specific interaction between SP65 and CD11c, CH223191 is specifically transported to DCs. This inhibits AhR function, promoting IL-12 and IFN-γ production in DCs and NK cells, respectively.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"683"},"PeriodicalIF":12.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292490","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":"Investigation of the effects of Si-A/PUE@HA hydrogels on the osteochondral defect microenvironment based on single-cell RNA sequencing.","authors":"Zhipeng Xi, Ning Xu, Xiaobo Zhou, Peng Chen, Yanwei He, Renwen Wan, Longlong Zhang, Zhipu Ding, Weiye Cai, Yisheng Chen, Zhiwen Luo, Wei Zhang, Chengshou Lin, Shuo Chen, Zhijie Zhao, Chao Liu, Jingchi Li","doi":"10.1186/s12951-025-03648-9","DOIUrl":"10.1186/s12951-025-03648-9","url":null,"abstract":"<p><p>Osteochondral defects pose significant challenges in joint health, leading to pain, decreased mobility, and substantial healthcare costs due to surgical interventions. This study aimed to develop and evaluate Si-A/PUE@HA composite hydrogels as scaffolding materials for cartilage tissue engineering, addressing the limitations of current treatment options. Utilizing a multi-step synthesis method that incorporates both chemical and physical crosslinking techniques, we assessed the hydrogels' cytocompatibility, chondrogenic differentiation potential, immunomodulatory properties, and in vivo cartilage regeneration capabilities. In vitro results demonstrated high cell viability and proliferation rates of bone marrow mesenchymal stem cells (BMSCs) cultured in Si-A/PUE@HA hydrogels, with significant expression of chondrogenic markers such as Acan, Sox9, and Col2a1. Notably, the hydrogels exhibited a favorable immunomodulatory effect, promoting an anti-inflammatory M2 macrophage phenotype, which is crucial for tissue regeneration. In vivo studies confirmed substantial new tissue formation and integration with surrounding cartilage, as evidenced by micro-CT analysis, alongside excellent biocompatibility with no significant adverse effects observed in major organs over a 12-week period. Single-cell RNA sequencing analysis revealed a favorable immune microenvironment and enhanced chondrogenesis linked to hydrogel treatment. In conclusion, Si-A/PUE@HA hydrogels represent a promising biomaterial with potential applications in cartilage repair and regenerative medicine, warranting further investigation in larger clinical trials to validate their efficacy and safety for future therapeutic use.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"680"},"PeriodicalIF":12.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292506","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":"Correction: Single‑cell multi‑omics analysis reveals the mechanism of action of a novel antioxidant polyphenol nanoparticle loaded with STAT3 agonist in mediating cardiomyocyte ferroptosis to ameliorate age‑related heart failure.","authors":"Haoyuan Zheng, Yuan Tian, Dongyu Li, Yanxiao Liang","doi":"10.1186/s12951-025-03739-7","DOIUrl":"10.1186/s12951-025-03739-7","url":null,"abstract":"","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"674"},"PeriodicalIF":12.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286424","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":"Biomimetic ferritin nanocages for synergistic co-delivery of metformin and rapamycin restore neurodevelopmental homeostasis in autism spectrum disorders.","authors":"Yizhe Shen, Lele Yu, Liujiao Wang, Jilu Jin, Cheng Yu, Yuan Fan, Yue Lang, Huashan Xu, Byron C Jones, Yishi Liu, Jiaying Wu, Siyuan Gao, Fuxue Chen, Shini Feng","doi":"10.1186/s12951-025-03760-w","DOIUrl":"10.1186/s12951-025-03760-w","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder with limited treatment options, largely due to its complex etiology and the inadequate delivery of therapeutics to the central nervous system. Herein, we report a novel biomimetic nanocomposite, HFn@M/R, designed for the synergistic co-delivery of metformin (Met) and rapamycin (Rapa) to restore neurodevelopmental homeostasis in ASD. Heavy-chain ferritin (HFn) nanocages, produced via an Escherichia coli expression system, were employed as a dual-drug carrier owing to their high drug loading capacity and intrinsic blood-brain barrier permeability via transferrin receptor 1 targeting. Comprehensive physicochemical characterization confirmed structural integrity, optimal drug loading, and redox/pH-responsive release under pathological conditions. In neuronal models, HFn@M/R restored mitochondrial membrane potential, enhanced AMPK-CREB-BDNF signaling, and suppressed mTOR hyperactivation and autophagic blockade. In a valproic acid-induced rat model of ASD, HFn@M/R achieved robust brain accumulation, ameliorated behavioral deficits, and normalized hippocampal electroencephalogram patterns. Transcriptomic analyses further revealed that HFn@M/R modulated key neurodevelopmental, metabolic, and immune pathways, underscoring its capacity to orchestrate a multi-target therapeutic network. Collectively, our findings establish HFn@M/R as a promising precision nanomedicine platform for ASD treatment, with potential applicability to a broad range of neurodevelopmental and neuroinflammatory disorders.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"670"},"PeriodicalIF":12.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286444","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}