Journal of Nanobiotechnology最新文献

{"title":"Hyaluronic acid-tailored prodrug nanoplatforms for efficiently overcoming colorectal cancer chemoresistance and recurrence by synergistic inhibition of cancer cell stemness.","authors":"Xirui Duan, Hailong Tian, Peilan Peng, Ping Zhou, Ning Ding, Guowen Liu, Gary T Bentley, Canhua Huang, Jun Yang, Ke Xie","doi":"10.1186/s12951-025-03484-x","DOIUrl":"10.1186/s12951-025-03484-x","url":null,"abstract":"<p><p>A subset of residual colorectal cancer (CRC) cells with stemness features exhibits a transient adaptive resistance after chemotherapy, limiting durable therapeutic benefits and even accelerating tumor recurrence. To tackle this problem, we have developed a targeted polymer prodrug nanoplatform (CHH-T/NPs) capable of synergistically inhibiting cancer cell stemness by modulating intracellular metabolism and inhibiting protective autophagy. Hyaluronic acid (HA) acts as a tumor-targeting molecular backbone, α-cyanohydroxycinnamic acid (CHC) is an inhibitor of monocarboxylic acid transporter 1 (MCT1), and hydroxychloroquine sulfate (HCQ) is an inhibitor of autophagy. These compounds were loaded on the HA backbone to form a polymeric prodrug, CHH, with pH-responsive ester bonds. CHH was self-assembled with mitochondria-targeting IR820 (T820), resulting in the formation of CHH-T/NPs. CHC and T820 disrupted cellular metabolism by inducing mitochondrial dysfunction and inhibiting lactate transport, leading to a synergistic inhibition of cancer cell stemness. Simultaneously, HCQ effectively inhibited autophagy to disrupt the self-protection mechanism of CRC cells. As anticipated, CHH-T/NPs effectively suppressed the chemoresistance and postoperative recurrence of CRC in subcutaneous and in situ tumors models. Taken together, this approach presents a promising strategy for overcoming CRC chemoresistance and recurrence through the synergistic inhibition of cancer cell stemness.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"507"},"PeriodicalIF":10.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637250","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":"Molecular mechanism differences between nanoplastics and microplastics in colon toxicity: nanoplastics induce ferroptosis-mediated immunogenic cell death, while microplastics cause cell metabolic reprogramming.","authors":"Yixian Cheng, Junjie Chen, Rui Fu, Peng Zhang, Haosong Chen, Haikun Cao, Zilong Jiang, Yuan Hong, Yifan Li, Cuiqi He, Fengjie Tao, Ting Li, Jiawei Zhang, Bo Chen, Guodong Cao","doi":"10.1186/s12951-025-03545-1","DOIUrl":"10.1186/s12951-025-03545-1","url":null,"abstract":"","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"505"},"PeriodicalIF":10.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637251","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":"Human adipose-derived mesenchymal stem cell-derived exosomes induce epithelial remodeling and anti-scar healing revealed by single-cell RNA sequencing.","authors":"Yu Fu, Jun-Ling Xie, Xing-Liao Zhang, Guang-Ming Xie, Xin-Min Zhang, Yao-Ting Han, Meng-Meng Xu, Jing Zhang, Jun Zhang","doi":"10.1186/s12951-025-03548-y","DOIUrl":"10.1186/s12951-025-03548-y","url":null,"abstract":"<p><p>The scar-free healing remains a clinical challenge, and requires the concerted efforts of multiple cell types, such as keratinocytes and fibroblasts. Exosomes derived from human adipose-derived mesenchymal stem cells (hADSC-Exos) have emerged as a promising therapeutic option. Nonetheless, a thorough understanding of the mechanisms underlying regenerative healing in response to hADSC-Exos treatment is still lacking. Here, we performed high-resolution single-cell RNA sequencing analysis of adult wild-type and hADSC-Exos-treated mice at postoperative day (POD) 14. hADSC-Exos influenced epithelial cells and fibroblasts, leading to scar-free wound healing. Among the epithelial cell subtypes, Lymphoid enhancer binding factor 1^high proliferating keratinocytes (prolif KC) are particularly remodeled by hADSC-Exos. Prolif KC exhibit epithelial-mesenchymal plasticity (EMP). Cell-cell communication between keratinocytes and fibroblasts during anti-scar healing is modulated by tumor growth factor-β1, which promotes the EMP transition cascade. hADSC-Exos may inhibit wound fibrosis through the 14-3-3 zeta-YES-associated protein-Hippo signaling pathway. This study enhances our understanding of epithelial cell diversity and interactions in wound healing, highlighting hADSC-Exo-induced prolif KC as a potential reprogramming target. These epithelial cells are promising therapeutic targets for improving wound-healing strategies.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"506"},"PeriodicalIF":10.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637249","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":"Targeted Inhibition of cGAS/STING signaling induced by aberrant R-Loops in the nucleus pulposus to alleviate cellular senescence and intervertebral disc degeneration.","authors":"Dan Wu, Chen Yan, Linhui Han, Fudong Li, Ximing Xu, Jingchuan Sun, Yong Cao, Kaiqiang Sun, Jiangang Shi, Yuan Wang","doi":"10.1186/s12951-025-03579-5","DOIUrl":"10.1186/s12951-025-03579-5","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IVDD) is a significant contributor to chronic low back pain and disability worldwide, yet effective treatment options remain limited. Through integrative analysis of single-cell RNA-seq data from intervertebral discs (IVDs), we have firstly uncovered that the aberrant accumulation of R-Loops-a type of triple-stranded nucleic acid structure-can result in the cytoplasmic accumulation of double-stranded DNA (dsDNA) and activate cGAS/STING signaling and induce cellular senescence in nucleus pulposus cells (NPCs) during IVDD. Restoring the R-Loop state significantly mitigated both the activation of the cGAS/STING pathway and NPC senescence. Additionally, we identified ERCC5 as a critical regulator of the R-Loop state and cellular senescence. Thus, we developed an NPC-targeting nano-delivery platform (CTP-PEG-PAMAM) to deliver si-Ercc5 to the NP region of the IVDD. This approach aims to modulate the abnormal R-Loop state and inhibit the activation of cGAS/STING signaling in NPCs for IVDD treatment. CTP-PEG-PAMAM demonstrated excellent targeting capability towards NPCs and NP tissue, and achieved effective silencing of the Ercc5 gene without causing systemic organ complications. Both in vitro and in vivo experiments revealed that CTP-PEG-PAMAM-siERCC5 significantly inhibited cGAS/STING signaling activated by aberrant R-Loops, alleviated cellular senescence and promoting cell proliferation, thereby delayed IVDD in a puncture-induced rat model. In conclusion, the ERCC5-R-Loop-cGAS/STING axis in NPCs represents a promising therapeutic target for delaying IVDD, and the designed CTP-PEG-PAMAM/siRNA complex holds great potential for clinical application in the treatment of IVDD.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"510"},"PeriodicalIF":10.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637271","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":"Engineered protein corona sustains stealth functionality of nanocarriers in plasma.","authors":"Xueqing Zhang, Shutian Si, Ingo Lieberwirth, Katharina Landfester, Volker Mailänder","doi":"10.1186/s12951-025-03565-x","DOIUrl":"10.1186/s12951-025-03565-x","url":null,"abstract":"","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"512"},"PeriodicalIF":10.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637248","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":"Near-infrared organic nanoparticles (6BQ NPs) enhance the random flaps survival by modulating the HSP90/HIF-1α axis through mild photothermal therapy.","authors":"Feng Wu, Jin Zhang, Jiangtian Ye, Jinwu Wang, Wenhao Zheng, Hua Chen, Xiaoyu Dong, Zu-Sheng Huang, Leyi Cai, Guangheng Xiang","doi":"10.1186/s12951-025-03570-0","DOIUrl":"10.1186/s12951-025-03570-0","url":null,"abstract":"<p><p>Random flaps are primarily employed in clinical practice for wound repair; however, the ischemic necrosis following surgery remains a significant challenge. To address this issue, we developed high-performance near-infrared (NIR) photothermal agent, 6BQ, to enhance random flaps survival through mild photothermal therapy (MPTT). In this study, we assessed the effects of 6BQ NPs on cell viability, proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) using MPTT in vitro. Techniques such as Cell Counting Kit-8(CCK8), wound scratch assay, Transwell assay, tube formation assay, RT-qPCR, and Western blotting were employed, along with an exploration of the related signaling mechanisms. In animal experiments, we utilized the McFarlane flap model in Sprague-Dawley rats, randomly assigning them to Control, 6BQ NPs, and 6BQ NPs + laser irradiation (6BQ NPs + L) groups. On postoperative day 7, we evaluated flap viability, assessed microcirculatory perfusion with laser Doppler flow imaging, and examined angiogenesis, inflammatory response, oxidative stress, and the activity of the Heat shock protein 90(HSP90)/ Hypoxia-inducible factor 1 alpha (HIF-1α) axis using immunological and molecular biological techniques. Results indicated that under 808 nm laser irradiation (0.5 W/cm², 15 min), 6BQ NPs activated the HSP90/HIF-1α axis through MPTT, promoting angiogenesis by upregulating Vascular endothelial growth factor (VEGF) expression. Concurrently, Superoxide dismutase (SOD) content increased while Malondialdehyde (MDA) content decreased through upregulation of Heme oxygenase-1(HO-1) expression, alleviating oxidative stress, and reduced Interleukin-6 (IL-6) and Tumor necrosis factor alpha (TNF-α) expression inhibited the inflammatory response, thereby significantly improving random flaps survival. In conclusion, this study highlights the potential of 6BQ NPs in improving random flaps survival, offering a novel therapeutic strategy for wound repair.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"503"},"PeriodicalIF":10.6,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618593","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":"FNDC5/irisin-enriched sEVs conjugated with bone-targeting aptamer alleviate osteoporosis: a potential alternative to exercise.","authors":"Min-Zhi Mao, Ming-Hui Zheng, Bei Guo, Ya-Li Ling, Xiao Lin, Fu-Xing-Zi Li, Su-Kang Shan, De-Xing Dai, Lei Qiu, Xue-Yang Cai, Ya Ding, Ying-Ying Gu, Qi-Rong Deng, Zhi-Ang Zhou, Li-Min Lei, Cheng Tao, Rong-Rong Cui, Feng Wu, Fei Zhang, Bo Wu, Le-Le Liao, Chang-Ming Tan, Xiao-Bo Liao, Ling-Qing Yuan, Feng Xu","doi":"10.1186/s12951-025-03587-5","DOIUrl":"10.1186/s12951-025-03587-5","url":null,"abstract":"<p><p>Exercise maintains bone health and produces protective effects on bone loss. In this study, we investigated the potential protective effects of circulating small extracellular vesicles (sEVs) generated under endurance exercise training (Exe-sEVs) on ovariectomized (OVX)-induced bone loss. Inhibition of sEVs secretion by GW4869 partially reversed exercised-induced protection against OVX-induced bone loss. Importantly, Exe-sEVs was internalized by bone tissue and alleviated bone loss in OVX-mice. The increased levels of fibronectin type-III domain-containing protein 5 (FNDC5/irisin) in Exe-sEVs contributed to the promotion of osteogenesis in bone marrow mesenchymal stem cells (BM-MSCs). However, systemic knockdown of FNDC5, the precursor of irisin, abolished the exercise-induced protective effects against bone loss in OVX-mice. Moreover, incubation of irisin enhanced osteogenesis and attenuated adipogenesis in BM-MSCs. Intriguingly, implantation of BM-MSCs overexpressing FNDC5 accelerated osteogenesis and chondrogenesis in BALB/c immunodeficiency mice. Mechanistically, irisin promoted phosphorylation of p38MAPK and JNK, but not ERK. Blocking the JNK and p38MAPK signaling pathway with specific inhibitors abolished the pro-osteogenesis and anti-adipogenesis effects of irisin on BM-MSCs. However, inhibition of β-arrestin-2 rescued the irisin-induced activation of p38MAPK and JNK. Finally, aptamer-modified FNDC5-sEVs (Apt-FNDC5-sEVs) exhibited higher enrichment in bone tissues and enhanced bone formation. In conclusion, exercise-induced circulating FNDC5/irisin-enriched sEVs promote osteogenesis of mouse BM-MSCs both in vitro and in vivo, partially through a β-arrestin-2-dependent p38MAPK and JNK signaling pathway. Apt-FNDC5-sEVs represent a promising strategy for the treatment of osteoporosis.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"504"},"PeriodicalIF":10.6,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618592","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":"USP5 inhibition via bone marrow-targeted engineered exosomes for myeloproliferative neoplasms therapy.","authors":"Wenjun Wang, Yufeng Jiang, Donglei Zhang, Xian Zhang, Qian Liang, Jun Shi, Yuan Zhou, Fuling Zhou","doi":"10.1186/s12951-025-03588-4","DOIUrl":"10.1186/s12951-025-03588-4","url":null,"abstract":"<p><p>Myeloproliferative neoplasms (MPNs) are challenging to treat due to the complex bone marrow (BM) microenvironment and lack of curative therapies. Current treatments fail to eliminate malignant clones and face issues like drug resistance. This study addressed these challenges by identifying USP5 as a critical regulator in JAK2^V617F-mutated mesenchymal stem cells (MSCs), which promotes proliferation by suppressing Caspase-3-mediated apoptosis. We developed engineered exosomes (USP5@Exosome-CP) co-expressing CXCR4 and a P-selectin-targeting peptide to enhance BM targeting. These exosomes, loaded with the USP5 inhibitor USP5-IN-1, demonstrated efficient BM homing and sustained drug release. In MPN mouse models, USP5@Exosome-CP significantly reduced MSC proliferation, extended survival, and showed minimal systemic toxicity. Transcriptomic analysis revealed that USP5 knockdown activated apoptosis pathways and suppressed oncogenic signaling. Our results establish USP5 as a therapeutic target and validate the engineered exosome platform as a promising strategy for MPN treatment, offering a blueprint for targeting other hematologic malignancies. This approach combines USP5 inhibition with BM-targeted nanotechnology, providing a proof-of-concept for personalized MPN therapy with improved efficacy and reduced off-target effects.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"501"},"PeriodicalIF":10.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618594","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":"Extracellular vesicles derived from Schwann cells to enhance bone and dental tissue regeneration: a literature review.","authors":"Xinyi Li, Minjia Zhu, Le Xiao, Jingyi Li, Kan Yu, Qinrou Zhang, Jialiang Dai, Zihan Jia, Zixiang Dai, Zheng Su, Ke Zhang, Yuxing Bai","doi":"10.1186/s12951-025-03585-7","DOIUrl":"10.1186/s12951-025-03585-7","url":null,"abstract":"<p><strong>Background: </strong>Recently, the importance and innovative applications of extracellular vesicles in bone and dental pulp tissue engineering have attracted more attention. Moreover, the use of extracellular vesicles derived from various cell types, such as mesenchymal stem cells, has been extensively examined. However, the understanding of the intricate mechanisms, diverse applications, and potential uses of extracellular vesicles originating from Schwann cells in neurogenesis, angiogenesis, neurovascularized osteogenesis, and dental pulp regeneration remains largely unexplored and under-investigated. This is the first review to provide a comprehensive overview of the cutting-edge researches on Schwann cell-derived extracellular vesicles (SCs-EVs) in the context of tissue regeneration. It emphasizes the emerging understanding of key bioactive molecules in SCs-EVs, including RNAs and proteins, and their role in promoting tissue regeneration. Furthermore, this review describes for the first time how bioactive molecules achieve neurogenic, angiogenic, osteogenic and odontogenic efficacy by activating related mechanistic pathways. In addition to these insights, the review also generalizes the potential clinical applications of SCs-EVs, both in the present and looking forward to future advancements in the field.</p><p><strong>Conclusions: </strong>SCs-EVs exhibit an impressive and effective capability for the delivery of RNAs and proteins, which play a crucial role in activating multiple biological mechanisms. Their remarkable combination with a diverse array of materials has demonstrated significant potential for facilitating tissue repair and regeneration across various biological systems. This review meticulously summarizes the various types of RNAs, proteins, and the related mechanisms that contribute to essential processes such as neurogenesis, angiogenesis, osteogenesis, and odontogenesis, highlighting their importance in regenerative medicine. Furthermore, we delve into the forefront of research and the potential applications of SCs-EVs specifically in the context of bone and dental tissue regeneration. The recent advancements in the development of SCs-EVs, alongside innovative biomaterial scaffolds, present a promising and transformative approach to enhancing therapeutic effectiveness in the regeneration of nerve, vascular, bone, and dental tissues, paving the way for future breakthroughs in regenerative therapies.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"502"},"PeriodicalIF":10.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618591","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":"Curcumin-based polymer prodrug nanoplatform for high-efficiency immunotherapy by synergistically suppression of head and neck cancer cell stemness.","authors":"Zhisen Shen, Hao Jiang, Shuaijun Lu, Hailong Tian, Feng Gao, Hongxia Deng, Canhua Huang","doi":"10.1186/s12951-025-03559-9","DOIUrl":"10.1186/s12951-025-03559-9","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy represents a transformative advance in cancer treatment; however, its efficacy in head and neck cancer (HNC) remains constrained by tumor cell stemness and profound immunosuppression within the tumor microenvironment (TME). Overcoming these barriers necessitates innovative strategies to simultaneously eradicate stem-like populations and reprogram the TME.</p><p><strong>Methods: </strong>We engineered a tumor-targeted polymer prodrug nanoplatform, Biotin@P-Cur/T780 NPs, integrating disulfide-linked polycurcumin (P-Cur) and the photothermal agent T780. DSPE-PEG-Biotin surface functionalization enables active tumor targeting. The nanoplatform exploits high intratumoral glutathione (GSH) to trigger disassembly, releasing curcumin monomers and T780. This elicits dual GSH depletion and reactive oxygen species (ROS) amplification, inducing ROS-mediated apoptosis and ferroptosis. Concurrently, localized near-infrared irradiation activates T780, synergizing photothermal (PTT) and photodynamic (PDT) therapies to intensify immunogenic cell death (ICD).</p><p><strong>Results: </strong>The Biotin@P-Cur/T780 NPs potently suppressed tumor cell stemness in vitro and in vivo. ROS/ferroptosis-driven ICD, amplified by PTT/PDT, reversed TME immunosuppression, enhancing dendritic cell maturation and cytotoxic T lymphocyte infiltration. This multimodal mechanism significantly inhibited primary tumor growth and metastasis in HNC models, while extending survival.</p><p><strong>Conclusion: </strong>Our prodrug nanoplatform overcomes key resistance mechanisms in HNC by coordinately targeting stemness, inducing dual apoptosis/ferroptosis, and potentiating ICD through PDT/PTT-enhanced immunomodulation. This strategy provides a potent combinatorial approach to augment immunotherapy efficacy in refractory tumors.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"500"},"PeriodicalIF":10.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618622","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}