{"title":"Genetically engineered Magnesium/Manganese nanoparticles for cancer radioimmunotherapy.","authors":"Jicheng Wu, Yangtao Xu, Yunjing Zhang, Kaixin Zhang, Jing Zhang, Yiming Guo, Peng She, Lang Rao, Ximing Xu","doi":"10.1186/s12951-025-03629-y","DOIUrl":"https://doi.org/10.1186/s12951-025-03629-y","url":null,"abstract":"<p><p>Radiotherapy (RT) has great potential on activating antitumor immunity for combination therapy, yet this effect is limited by immunosuppressive tumor microenvironment (TME) and the potential toxicity in immune cells from high-dose radiation. Herein, we developed engineered nanoparticles (NPs) (CVs@MgMn) composed of genetically edited cellular vesicles (CVs), MnO<sub>2</sub> and MgCO<sub>3</sub> for enhanced radioimmunotherapy by remolding TME and activating the stimulator of the interferon genes (STING) pathway. In the TME, the efficiently enriched CVs@MgMn were decomposed to generate hydroxyl (‧OH) and oxygen (O<sub>2</sub>) for radiosensitization. Subsequently, reduced Mn<sup>2+</sup> activated the STING pathway to promote dendritic cell (DC) maturation, and the released Mg<sup>2+</sup> boosted antitumor immunity by regulating CD8<sup>+</sup> T cell metabolism and tumor-associated macrophage polarization. PD1-displayed CVs increased the targeting effect of NPs and mediated the PD-L1 blocking, all synergistically triggering antitumor immune responses. In both in situ and distant re-challenge models of melanoma, the combination of RT and nanocomposites demonstrated a strong radioimmunotherapy effect, resulting in an increased survival time and long-term immunological memory of tumor bearing mice. Moreover, MgCO<sub>3</sub> NPs synergistically promoted anti-PD-1 mAb immunotherapy. These findings highlight the importance of Mg/Mn combined supplementation and TME remolding during RT and immunotherapy, offered a simple and readily therapeutic strategy for patients with any type of solid tumor.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"593"},"PeriodicalIF":12.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957529","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}
Ji-Eun Kim, Ye Eun Ji, Hyeon Jun Hwang, Ga-Eun Go, Hyung-Jun Lim, Jaein Yoo, Jooho Kim, Doil Park, Eun Hee Kim, Doory Kim, Oh Young Bang
{"title":"Engineered MSC-EVs loaded with BDNF-enhancing neuropeptides via a non-disruptive method enhance post-stroke neuroregeneration via intranasal delivery.","authors":"Ji-Eun Kim, Ye Eun Ji, Hyeon Jun Hwang, Ga-Eun Go, Hyung-Jun Lim, Jaein Yoo, Jooho Kim, Doil Park, Eun Hee Kim, Doory Kim, Oh Young Bang","doi":"10.1186/s12951-025-03654-x","DOIUrl":"https://doi.org/10.1186/s12951-025-03654-x","url":null,"abstract":"<p><p>Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) show potential as neuroregenerative therapies. Incorporating bioactive compounds such as neuropeptides that enhance brain-derived neurotrophic factor (BDNF) expression may amplify their therapeutic potential. We developed a clinical-scale method for loading neuropeptides into MSC-EVs, while preserving their structural integrity and therapeutic functionality. Through scalable 3D bioprocessing, we produced high-purity MSC-EVs and evaluated loading methods for encapsulating neuropeptides and full-length BDNF. EVs were characterized using electron microscopy, nanoparticle tracking analysis, and 3D STORM microscopy. The cellular uptake, distribution, and biological effects of neuropeptide-loaded MSC-EVs were tested in vitro and in vivo. Passive incubation was the optimal loading method for maintaining EV integrity while achieving effective neuropeptide encapsulation. Active loading methods destabilized the EV membrane despite higher encapsulation efficiency. Neuropeptide-loaded MSC-EVs crossed the blood-brain barrier (BBB) and significantly enhanced BDNF expression, neurogenesis, and neuroprotection in vitro, ex vivo, and in vivo. Compared with HEK293-derived extracellular vesicles (HEK-EVs), MSC-EVs demonstrated superior regenerative effects. In a photothrombotic stroke model, intranasal administration of neuropeptide-loaded MSC-EVs reduced infarct size, improved neuronal survival, and activated neuroprotective pathways mediated by Cyclic AMP Response Element-Binding protein (CREB) phosphorylation. We established a clinically scalable approach for producing neuropeptide-loaded MSC-EVs with potential as next-generation, targeted neuroregenerative therapies for treating stroke and other neurological disorders. Importantly, the EVs used in this study were produced under clinically applicable conditions and characterized according to the Minimal Information for Studies of Extracellular Vesicles (MISEV) 2023 guidelines.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"594"},"PeriodicalIF":12.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957523","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}
Guangwen Li, Yan Zhang, Haochen Wang, Yuqi Zhao, Kexin Liu, Zhe Li, Meng Meng, Yide He, Wen Song
{"title":"The bone marrow mesenchymal stem cells derived migrasomes induced by Titania nanotubes surface serve as chemotaxis effect for osteogenesis.","authors":"Guangwen Li, Yan Zhang, Haochen Wang, Yuqi Zhao, Kexin Liu, Zhe Li, Meng Meng, Yide He, Wen Song","doi":"10.1186/s12951-025-03641-2","DOIUrl":"https://doi.org/10.1186/s12951-025-03641-2","url":null,"abstract":"<p><p>The regulatory role of migrasomes (Migs) has attracted growing attentions recently. However, most of the reports only focus on the influence of donor cells on Migs contents, regarding the substrate information. In the present study, the bone marrow mesenchymal stem cells (BMSCs) derived Migs were investigated on titania micropits/nanotubes (MNT) under different anodization voltages. The Migs formation was dependent on nanotubes dimensions, which was the most dominant on MNT5 (anodization under 5 V) surface and in line with ITGA5 expression level. The cargo analysis revealed significant enrichment of chemotaxis, in which the CXCL12 and CCL2 were the top enriched. Afterwards, the Migs could induce similar chemotaxis effect of CXCL12/CXCR4 axis in BMSCs and ECs and CCL2/CCR2 axis in macrophages. Further, the engulfment of Migs could induce significant enhancement of BMSCs osteogenic differentiation, ECs tube formation and macrophages M2 polarization. The in vivo ectopic bone formation model was subcutaneous implantation of biphasic calcium phosphate (BCP)/acylated methacrylate gelatin (GelMA) composite hydrogel with or without Migs. The scaffold could induce abundant cells recruitment 7 days post implantation and the CD90<sup>+</sup> or CD31<sup>+</sup> cell populations were significantly increased in the presence of Migs. After implantation for 2 and 4 weeks, the new bone growth within scaffold was significantly increased by Migs incorporation, both around BCP backbone and in the space area. In addition, the new bone area showed significant upregulation of CD163, CD31 and OSX. In conclusion, the titania nanotubes induced Migs from BMSCs could both recruit regenerative cells and directly promote osteogenesis, which may represent a new type of therapeutic EVs in bone tissue engineering.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"592"},"PeriodicalIF":12.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957612","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}
Shijie Yao, Yinan Wang, Liqiang Shao, Yang Chen, Aodi Niu, Junjia He, Weijiao Fan, Liang Xu, Bai Xu, Xiaozhou Mou, Xianghong Yang, Yu Cai
{"title":"Injured renal cell membrane encapsulated ICG/CORM-401 for homologous targeted NIR theranostics of acute kidney injury.","authors":"Shijie Yao, Yinan Wang, Liqiang Shao, Yang Chen, Aodi Niu, Junjia He, Weijiao Fan, Liang Xu, Bai Xu, Xiaozhou Mou, Xianghong Yang, Yu Cai","doi":"10.1186/s12951-025-03634-1","DOIUrl":"https://doi.org/10.1186/s12951-025-03634-1","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is frequently attributed to the lack of effective early diagnosis and incorrect timing for treatment, resulting in a high incidence rate and mortality. Currently, there is no precise clinical treatment available for AKI. In this study, we developed a good approach utilizing injured renal cell membrane-coated ICG/CORM-401 nanosystem (IRICP), which can specifically target to the injured kidney site through homologous targeting of the injured renal cell membrane. Through in vivo experiments, we demonstrated that indocyanine green (ICG), acting as a near-infrared (NIR) contrast agent, enables clear visualization of its distribution using fluorescence imaging and photoacoustic imaging (PAI) techniques. The addition of CORM-401 effectively mitigates AKI-induced oxidative stress by consuming reactive oxygen species and generating carbon monoxide for anti-inflammatory, anti-apoptotic, and anti-oxidative effects, thereby effectively inhibiting the progression of AKI and facilitating its recovery. In conclusion, this targeted theranostic strategy presents high efficiency and promise potential for the future clinical treatment of AKI.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"589"},"PeriodicalIF":12.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957559","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}
Ji Chen, Lin Zhu, Yangyuxi Chen, Yuan Liu, Wen Chen, Xinxin Liu, Fengrui Yang
{"title":"Targeted neural stem cell-derived extracellular vesicles loaded with Sinomenine alleviate diabetic peripheral neuropathy via WNT5a/TRPV1 pathway modulation.","authors":"Ji Chen, Lin Zhu, Yangyuxi Chen, Yuan Liu, Wen Chen, Xinxin Liu, Fengrui Yang","doi":"10.1186/s12951-025-03678-3","DOIUrl":"https://doi.org/10.1186/s12951-025-03678-3","url":null,"abstract":"<p><strong>Background: </strong>Diabetic peripheral neuropathy (DPN) is one of the most prevalent and debilitating complications of diabetes, marked by chronic neuroinflammation, immune dysregulation, and progressive neuronal degeneration. Current treatments offer limited efficacy, largely focusing on symptomatic relief rather than addressing the underlying disease mechanisms. There is a critical need for disease-modifying therapies that target the molecular basis of DPN.</p><p><strong>Results: </strong>In this study, we developed a novel targeted nanotherapeutic system-ZH-1c-EVs@SIN-composed of neural stem cell-derived extracellular vesicles (NSC-EVs) modified with the ZH-1c aptamer and loaded with the anti-inflammatory compound sinomenine (SIN). This system was specifically designed to target microglia and inhibit the WNT5a/TRPV1 signaling pathway. Transcriptomic profiling of microglia revealed key gene networks implicated in DPN pathology and responsive to SIN treatment. Functional assays demonstrated that ZH-1c-EVs@SIN facilitated a shift in microglial phenotype from pro-inflammatory M1 to anti-inflammatory M2, significantly reduced inflammatory cytokine expression, and restored levels of neuronal regulatory proteins. Nanoparticle tracking analysis and transmission electron microscopy confirmed optimal vesicle size and morphology, while fluorescence imaging showed efficient uptake by microglia. In vivo studies in a murine model of DPN revealed marked improvements in pain-related behavior and histopathological signs of nerve damage.</p><p><strong>Conclusion: </strong>ZH-1c-EVs@SIN represents a promising therapeutic strategy for DPN, offering targeted immunomodulation and enhanced neural repair via regulation of the WNT5a/TRPV1 signaling axis. This nano-delivery platform introduces a novel and precise approach to intervening in diabetic neuropathy and may be applicable to other neuroinflammatory conditions.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"588"},"PeriodicalIF":12.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957618","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}
Anastasia Chillà, Cecilia Anceschi, Francesca Scavone, Serena Martinelli, Jessica Ruzzolini, Elena Frediani, Francesca Margheri, Tahir Tahir, Guilherme C Concas, Mariana Gisbert, Marco Cremona, Fernando Freire, Ricardo Q Aucélio, Tatiana Saint Pierre, André L Rossi, Mirko Severi, Rita Traversi, Daniele Bani, Daniele Guasti, Nicola Daldosso, Mario Del Rosso, Gabriella Fibbi, Celso SantAnna, Tommaso Del Rosso, Anna Laurenzana
{"title":"Sparking angiogenesis by carbon monoxide-rich gold nanoparticles obtained by pulsed laser driven CO<sub>2</sub> reduction reaction.","authors":"Anastasia Chillà, Cecilia Anceschi, Francesca Scavone, Serena Martinelli, Jessica Ruzzolini, Elena Frediani, Francesca Margheri, Tahir Tahir, Guilherme C Concas, Mariana Gisbert, Marco Cremona, Fernando Freire, Ricardo Q Aucélio, Tatiana Saint Pierre, André L Rossi, Mirko Severi, Rita Traversi, Daniele Bani, Daniele Guasti, Nicola Daldosso, Mario Del Rosso, Gabriella Fibbi, Celso SantAnna, Tommaso Del Rosso, Anna Laurenzana","doi":"10.1186/s12951-025-03680-9","DOIUrl":"https://doi.org/10.1186/s12951-025-03680-9","url":null,"abstract":"<p><p>Endothelial tissue regeneration is a major challenge in the context of vascular disorders and tissue repair. One of the most recent and promising therapies for endothelial tissue disorders is the administration of carbon monoxide (CO) by direct injection or release by CO-releasing molecules (CORMs). Despite the great potential of CORMs, light instability and cytotoxicity associated with the heavy metal core are still major drawbacks that inhibit clinical application. Recently, we have shown the possibility to synthesize carbon monoxide rich gold nanoparticles (CO-rich AuNPs) by the pulsed laser driven CO<sub>2</sub> reduction reaction in water. In this work, we investigate the potential of this unique metal-organic complex as a therapeutic approach to promote endothelial tissue regeneration, by performing a comparative analysis between the CO releasing potential of CO-rich AuNPs and a well-known CO-releasing molecule, specifically CORM-2. Through a combination of in vitro and in vivo experiments, we elucidated the mechanisms by which the laser synthesized ligand-free or CO-rich AuNPs inhibit or enhance, respectively, the endothelial cell migration and angiogenesis. Notably, the biocompatible CO-rich AuNPs not only boost these cellular processes but also play a pivotal role in triggering histone acetylation, shedding light on an additional regulatory pathway.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"590"},"PeriodicalIF":12.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957662","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}
Ye Zhao, Jinchen He, Yuxi Liu, Hassna Soummane, Pan Ran, Qian Yang, Xiaofang Gao, Wenxiong Cao, Long Zhao
{"title":"Ultrasound-actuated platelet mimetic nanomotors enable targeted piezocatalytic ROS storm for precision thrombolysis.","authors":"Ye Zhao, Jinchen He, Yuxi Liu, Hassna Soummane, Pan Ran, Qian Yang, Xiaofang Gao, Wenxiong Cao, Long Zhao","doi":"10.1186/s12951-025-03675-6","DOIUrl":"https://doi.org/10.1186/s12951-025-03675-6","url":null,"abstract":"<p><p>Thrombotic diseases pose life-threatening risks, yet current thrombolytic therapies face limitations including poor targeting and bleeding risks. To address this, ultrasound-activatable nanomotors (hBT-Pt@Pm) were developed through the integration of hollow BaTiO₃/Pt Schottky heterojunctions with platelet membrane (Pm) coatings. The hollow structure enhances piezocatalytic efficiency by shortening charge migration distances, while Pt deposition improves carrier separation, collectively boosting reactive oxygen species (ROS) generation under ultrasound. Finite element simulations confirmed a 5.8-fold increase in piezoelectric potential compared to solid BaTiO₃. Asymmetric Pt caps enable cavitation-driven thrombus penetration, and Pt-mediated H₂O₂ decomposition generates O₂ bubbles to amplify ROS production. In vitro, Pm coating conferred 5.2-fold higher thrombus accumulation than non-targeted nanoparticles. In murine venous thrombosis models, the nanomotors achieved near-complete clot dissolution via synergistic piezocatalysis and mechanical penetration, without systemic toxicity. This approach provides a targeted, ultrasound-powered alternative to conventional thrombolytics, combining precision therapy with inherent biosafety.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"585"},"PeriodicalIF":12.6,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957626","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":"Lithium-doped calcium silicate scaffolds-activated M2-polarized macrophage-derived miR-145-5p-riched extracellular vesicles to enhance osteoimmunomodulation for accelerating bone regeneration.","authors":"Ting-You Kuo, Tsung-Li Lin, Yen-Hong Lin, Cheng-Yu Chen, Der-Yang Cho, Yi-Wen Chen, Ming-You Shie","doi":"10.1186/s12951-025-03679-2","DOIUrl":"10.1186/s12951-025-03679-2","url":null,"abstract":"<p><p>Bone healing is intricately associated with dynamic macrophage polarization. Modulating macrophages toward the M2 phenotype has emerged as a promising strategy in bone tissue engineering. Calcium silicate, known for its superior osteoconductivity, is widely used as a bone substitute and is particularly effective in promoting bone tissue regeneration when incorporated with bioactive ions. Recent studies have highlighted lithium's immunomodulatory effects, with extracellular vesicles (EVs) identified as potential mediators of these actions. Although M2 macrophage-derived EVs (M2-EVs) have been shown to promote bone regeneration, the underlying mechanisms through which biomaterial-stimulated M2-EVs regulate bone regeneration remain unclear. This study investigated the immunomodulatory effects of lithium-doped calcium silicate (LiCS) scaffolds on macrophages and associated inflammatory cytokine profiles. Notably, miR-145-5p was significantly upregulated in both LiCS-stimulated macrophages and their secreted EVs, suggesting a potential regulatory role. Characterization of these miR-145-5p-enriched EVs revealed enhanced anti-inflammatory responses, stimulation of angiogenesis, and upregulation of osteogenic markers in relation to M1 macrophages, mesenchymal stem cells, and endothelial cells. These findings elucidate the molecular basis of LiCS-stimulated M2-EV-regulated bone regeneration via miR-145-5p, providing new insights into developing immunomodulatory biomaterials in regenerative medicine.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"586"},"PeriodicalIF":12.6,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957606","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}
Yu Peng, Zhe Li, Lei Zhou, Qian Jian, Baoli Yin, Bo Sun, Yinghui Song, Hao Chen, Xianzheng Tan, Xiaohui Duan, Sulai Liu, Chuang Peng, Guosheng Song
{"title":"Drug repurposing: isosorbide mononitrate enhances tumor accumulation to augment sonodynamic therapy for hepatocellular carcinoma.","authors":"Yu Peng, Zhe Li, Lei Zhou, Qian Jian, Baoli Yin, Bo Sun, Yinghui Song, Hao Chen, Xianzheng Tan, Xiaohui Duan, Sulai Liu, Chuang Peng, Guosheng Song","doi":"10.1186/s12951-025-03674-7","DOIUrl":"https://doi.org/10.1186/s12951-025-03674-7","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a leading cause of cancer death worldwide. Sonodynamic therapy (SDT) offers a non-invasive, deep-penetrating approach by using ultrasound to activate sonosensitizers and generate cytotoxic reactive oxygen species (ROS). Yet poor intratumoral delivery and low ROS quantum yields of existing agents have stalled clinical translation. Here, we present a synergistic SDT platform that overcomes these barriers by combining transient vasodilation of tumor microvessels with the clinically widely used Antianginal drug isosorbide mononitrate and an acceptor-donor-acceptor-donor-acceptor type organic nanosonosensitizer (BTz) engineered for a narrow bandgap and enhanced ultrasound responsiveness. Isosorbide mononitrate increases nanosonosensitizer accumulation by ~ 1.8-fold. Under ultrasound irradiation, nanosonosensitizer produced high ROS generation, resulting in 78% tumor growth inhibition in murine HCC models-nearly double that of SDT alone-without detectable systemic toxicity. Crucially, the near-infrared fluorescence of nanosonosensitizer enabled real-time, image-guided tracking of sonosensitizer uptake and therapeutic response. By repurposing a safe vasodilator and integrating it with a high-performance organic sonosensitizer, this work establishes a readily translatable, minimally invasive paradigm for precise SDT of localized, inoperable or metastatic HCC.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"587"},"PeriodicalIF":12.6,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957496","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}