Journal of Nanobiotechnology最新文献

{"title":"Injectable celastrol-loading emulsion hydrogel for immunotherapy of low-immunogenic cancer.","authors":"Yu Liu, Jia Zhang, Chunyu Lai, Wenjun Wang, Yangyue Huang, Xuanwen Bao, Haimeng Yan, Xuqi Sun, Qiqi Liu, Dong Chen, Xiaomeng Dai, Xinyu Qian, Peng Zhao","doi":"10.1186/s12951-025-03154-y","DOIUrl":"10.1186/s12951-025-03154-y","url":null,"abstract":"<p><p>Immunotherapy, exemplified by immune checkpoint blockade (ICB), has been extensively employed in antitumor treatments. Nevertheless, its efficacy in addressing low-immunogenic tumors has not yielded satisfactory results, primarily due to the depletion and inadequate infiltration of effector T cells within the tumor microenvironment (TME). Here, we construct an injectable water-in-oil emulsion hydrogel to load clinically used Celastrol (Gel@Cel), which addresses the limitations of Cel's hydrophobicity. Cel can both inhibit tumor cell proliferation and promote tumor cell apoptosis, while simultaneously inducing immunogenic cell death, through activation of the AKT and MAPK pathways. In a model of clinically refractory hepatocellular carcinoma with malignant ascites, intraperitoneal administration of Gel@Cel significantly inhibits tumor progression and activates antitumor immune effects through lipase-controlled release of Cel, as compared to free Cel. Intriguingly, the Gel@Cel induces the activation of dendritic cells, resulting in the infiltration of cytotoxic T cells in the TME of ascites. Furthermore, the administration of Cel increases the expression of programmed cell death protein ligand-1 (PD-L1) in tumor cells. Moreover, combining the PD-1 antibody (αPD-1) with Gel@Cel further enhances the antitumor effect and amplifies the immune activation. In conclusion, Gel@Cel exhibits promising therapeutic potential in the treatment of low-immunogenic tumors, especially when combined with ICB therapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"183"},"PeriodicalIF":10.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573112","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":"Regulating macrophage phenotypes with IL4I1-mimetic nanoparticles in IDD treatment.","authors":"Jiaying Luo, Guoxin Jin, Shaoqian Cui, Huan Wang, Qi Liu","doi":"10.1186/s12951-025-03241-0","DOIUrl":"10.1186/s12951-025-03241-0","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IDD) is a degenerative spinal condition characterized by disc structural damage, narrowing of joint spaces, and nerve root compression, significantly reducing patients' quality of life. To address this challenge, a novel therapeutic strategy was developed using cellulose supramolecular hydrogel as a carrier to deliver IL4I1-modified MΦ membrane biomimetic nanoparticles (CHG@IL4I1-MNPs) to target tissues. This hydrogel exhibits excellent biocompatibility and mechanical properties while enabling sustained drug release in the degenerative disc microenvironment, enhancing therapeutic outcomes. CHG@IL4I1-MNPs effectively regulate MΦ polarization by promoting M2 MΦ activation, thereby improving immune microenvironment balance. Animal studies demonstrated that CHG@IL4I1-MNPs alleviated symptoms of IDD, reduced inflammation, and supported tissue repair, highlighting its potential to reduce reliance on long-term medication and improve quality of life. The strategy uniquely combines nanoparticle technology with immunomodulation, achieving precise targeting of MΦs. Beyond IDD, this approach offers potential applications in other immune-related diseases, providing a versatile platform for nanomedicine. This study introduces an innovative method to treat IDD and advances the integration of immunotherapy and nanotechnology, offering both clinical benefits and new directions for future research. These findings hold strong potential for improving patient outcomes and expanding treatment options for related diseases.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"175"},"PeriodicalIF":10.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573133","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":"Responsive nanoparticles synergize with Curcumin to break the \"reactive oxygen Species-Neuroinflammation\" vicious cycle, enhancing traumatic brain injury outcomes.","authors":"Xianhua Fu, Yongkang Zhang, Guojie Chen, Guangyao Mao, Jiajia Tang, Jin Xu, Yuhan Han, Honglin Chen, Lianshu Ding","doi":"10.1186/s12951-025-03251-y","DOIUrl":"10.1186/s12951-025-03251-y","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) disrupts oxygen homeostasis in the brain, leading to excessive reactive oxygen species (ROS) production and dysregulated antioxidant mechanisms, which fail to clear excess ROS. This ROS overload promotes the expression of pro-inflammatory genes, releasing cytokines and chemokines and creating a vicious \"ROS-neuroinflammation\" cycle, making it essential to break this cycle for effective TBI treatment. In this study, we developed cysteine-alanine-glutamine-lysine (CAQK) peptide-modified antioxidant nanoparticles (C-PPS/C) for co-delivery of curcumin (Cur) to modulate oxidative and neuroinflammatory disturbances after TBI. In TBI mice, C-PPS/C nanoparticles accumulated in injured brain regions, where poly (propylene sulfide)₁₂₀ scavenged ROS, reducing oxidative stress, while Cur release further suppressed ROS and inflammation. C-PPS/C nanoparticles broke the \"ROS-neuroinflammation\" cycle, protecting the blood-brain barrier (BBB), reducing acute brain edema, and promoting long-term neurological recovery. Further investigation showed that C-PPS/C nanoparticles inhibited the NF-κB pathway, reducing pro-inflammatory gene expression and mitigating inflammation, suggesting a promising approach for TBI treatment.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"172"},"PeriodicalIF":10.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567205","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":"An anti-CD19-exosome delivery system navigates the blood-brain barrier for targeting of central nervous system lymphoma.","authors":"Meifang Zhao, Qi Li, Yali Chai, Rong Rong, Lexin He, Yuchen Zhang, Hongxia Cui, Hao Xu, Xinyun Zhang, Zhiming Wang, Shushu Yuan, Menglu Chen, Chuan He, Han Zhang, Linlin Qin, Ruijing Hu, Xinyuan Zhang, Wenzhuo Zhuang, Bingzong Li","doi":"10.1186/s12951-025-03238-9","DOIUrl":"10.1186/s12951-025-03238-9","url":null,"abstract":"<p><strong>Background: </strong>High-dose methotrexate (HD-MTX) serves as the cornerstone of central nervous system lymphoma (CNSL) treatment, but its efficacy is limited due to low blood-brain barrier (BBB) penetration and adverse effects. This study is focused on an exosome-based drug delivery approach aimed at enhancing BBB permeability, thereby reducing the required dosage of methotrexate (MTX) while ensuring specific targeting of CNSL.</p><p><strong>Methods: </strong>Human adipose-derived mesenchymal stem cells (hAMSCs) were modified with a lentiviral vector encoding anti-CD19, incorporated into exosomes characterized by colloidal gold immunoelectron microscopy and Nano flow cytometry. MTX loaded into anti-CD19-Exos via co-incubation, assessed for loading and encapsulation efficiencies using HPLC. In vitro BBB model constructed using hCMEC/D3 and astrocytes to investigate BBB permeability. In vivo efficacy of anti-CD19-Exo-MTX evaluated in intracranial CNSL models using MRI. Biodistribution tracked with DiR-labeled exosomes, drug concentration in CSF measured by HPLC. LC-MS/MS identified and characterized exosomal proteins analyzed using GO Analysis. Neuroprotective effects of exosomal proteins assessed with TUNEL and Nissl staining on hippocampal neurons in CNSL models. Liver and kidney pathology, blood biochemical markers, and complete blood count evaluated exosomal protein effects on organ protection and MTX-induced myelosuppression.</p><p><strong>Results: </strong>We generated anti-CD19-Exo derived from hAMSCs. These adapted exosomes effectively encapsulated MTX, enhancing drug accessibility within lymphoma cells and sustained intracellular accumulation over an extended period. Notably, anti-CD19-Exo-MTX interacted with cerebrovascular endothelial cells and astrocytes of the BBB, leading to endocytosis and facilitating the transportation of MTX across the barrier. Anti-CD19-Exo-MTX outperformed free MTX in vitro, exhibiting a more potent lymphoma-suppressive effect (P < 0.05). In intracranial orthotopic CNSL models, anti-CD19-Exo-MTX exhibited a significantly reduced disease burden compared to both the MTX and Exo-MTX groups, along with prolonged overall survival (P < 0.05). CSF drug concentration analysis demonstrated enhanced stability and longer-lasting drug levels for anti-CD19-Exo-MTX. Anti-CD19-Exo-MTX exhibited precise CNSL targeting with no organ toxicity. Notably, our study highlighted the functional potential of reversal effect of hAMSCs-exosomes on MTX-induced neurotoxicity, hepatic and renal impairment, and myelosuppression.</p><p><strong>Conclusions: </strong>We present anti-CD19-Exo-MTX as a promising exosome-based drug delivery platform that enhances BBB permeability and offers specific targeting for effective CNSL treatment with reduced adverse effects.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"173"},"PeriodicalIF":10.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567265","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":"Nanophotonic-enhanced photoacoustic imaging for brain tumor detection.","authors":"Ali Rizwan, Badrinathan Sridharan, Jin Hyeong Park, Daehun Kim, Jean-Claude Vial, Kwangseuk Kyhm, Hae Gyun Lim","doi":"10.1186/s12951-025-03204-5","DOIUrl":"10.1186/s12951-025-03204-5","url":null,"abstract":"<p><p>Photoacoustic brain imaging (PABI) has emerged as a promising biomedical imaging modality, combining high contrast of optical imaging with deep tissue penetration of ultrasound imaging. This review explores the application of photoacoustic imaging in brain tumor imaging, highlighting the synergy between nanomaterials and state of the art optical techniques to achieve high-resolution imaging of deeper brain tissues. PABI leverages the photoacoustic effect, where absorbed light energy causes thermoelastic expansion, generating ultrasound waves that are detected and converted into images. This technique enables precise diagnosis, therapy monitoring, and enhanced clinical screening, specifically in the management of complex diseases such as breast cancer, lymphatic disorder, and neurological conditions. Despite integration of photoacoustic agents and ultrasound radiation, providing a comprehensive overview of current methodologies, major obstacles in brain tumor treatment, and future directions for improving diagnostic and therapeutic outcomes. The review underscores the significance of PABI as a robust research tool and medical method, with the potential to revolutionize brain disease diagnosis and treatment.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"170"},"PeriodicalIF":10.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567268","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":"NebulaPlate: a droplet microfluidic platform to analyze platelet aggregation.","authors":"Zheyi Jiang, Meng Wei, Jiawei Zhu, Chenguang Wang, Tiantian Zhang, Wenjie Zhu, Rong Zhang, Kandi Zhang, Peng Zhang, Yihua Lu, Alex Chia Yu Chang, Yifan Liu, Junfeng Zhang","doi":"10.1186/s12951-025-03212-5","DOIUrl":"10.1186/s12951-025-03212-5","url":null,"abstract":"<p><p>The accurate assessment of platelet activity is crucial in clinical practice and scientific research owing to the pivotal role of platelets in the progression of cardiovascular conditions, such as arterial thrombotic diseases. However, conventional platelet activity assessment methods are currently limited by their requirement of substantial blood samples and inadequate high-throughput capabilities, and therapeutic resistance induced by antiplatelet agents impedes treatment efficacy. In this study, we developed a microdroplet-based platelet function detection method, referred to as NebulaPlate, to achieve miniaturized and robust platelet activity assessment, thereby overcoming current challenges. NebulaPlate supports the merging of platelet samples with drugs confined in picoliter microdroplets and leverages an imaging-based analysis to automatically identify platelets, evaluate their aggregation, and determine P-selectin expression within the anchored microdroplets. We experimentally confirmed the feasibility of aggregation assays on NebulaPlate using various representative antiplatelet drugs. Requiring only 0.3 mL whole blood/chip, which corresponds to approximately 100 platelets/reaction, NebulaPlate reduced the consumption of platelet samples in a single assay. This represents a reduction of 10 times compared to that of conventional techniques. Moreover, our experimental results confirmed the validity and reproducibility of platelet function assays performed using NebulaPlate. Our research highlights important developments in the field of platelet activity assessment and provides fresh prospects for future antiplatelet therapies and personalized medicine. Moreover, it introduces new possibilities for research and clinical practice related to arterial thrombotic diseases.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"171"},"PeriodicalIF":10.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567283","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":"Infertility treatment using polysaccharides-based hydrogels: new strategies in tissue engineering and regenerative medicine.","authors":"Maryam Ghahremani-Nasab, Soraya Babaie, Sara Bazdar, Ana Cláudia Paiva-Santos, Mahdiyeh Rahmani Del Bakhshayesh, Naeimeh Akbari-Gharalari, Sonia Fathi-Karkan, Diba Ghasemi, Azizeh Rahmani Del Bakhshayesh","doi":"10.1186/s12951-025-03267-4","DOIUrl":"10.1186/s12951-025-03267-4","url":null,"abstract":"<p><p>Infertility is a primary health issue affecting about 15% of couples of reproductive ages worldwide, leading to physical, mental, and social challenges. Advances in nanobiotechnology and regenerative medicine are opening new therapeutic horizons for infertility by developing polysaccharide-based nanostructured biomaterials. This review explores the role of tissue engineering and regenerative medicine in infertility treatment, explicitly focusing on the promising potential of polysaccharide-based hydrogels. In this context, using these biomaterials offers unique advantages, including biodegradability, biocompatibility, and the ability to mimic the natural endometrial microenvironment, making them highly effective for applications in endometrial regeneration, ovarian tissue engineering, spermatogenesis support, and controlled drug delivery. This review discusses the various properties and uses of polysaccharide-based hydrogels, like alginate, hyaluronic acid, and chitosan, in helping to restore reproductive function. While these materials hold great promise, some notable challenges to their clinical use include issues like rapid degradation, mechanical instability, and potential immune reactions. Future research should focus on developing hybrid hydrogels, investigating advanced fabrication techniques, and testing these materials in clinical settings. By combining findings from recent studies, this review aims to provide a solid foundation for researchers and clinicians looking to discover new and effective strategies for treating infertility, ultimately connecting research efforts with practical applications in healthcare.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"162"},"PeriodicalIF":10.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542283","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":"Naringenin cationic lipid-modified nanoparticles mitigate MASLD progression by modulating lipid homeostasis and gut microbiota.","authors":"Lu Dong, Wenyong Lou, Congfei Xu, Juan Wang","doi":"10.1186/s12951-025-03228-x","DOIUrl":"10.1186/s12951-025-03228-x","url":null,"abstract":"<p><p>Naringenin (NAR) possesses various pharmacological activities including antioxidant, anti-inflammatory, and hepatoprotective effects. However, its therapeutic efficacy is limited by its hydrophobic and crystalline nature. This study aimed to investigate the therapeutic potential and molecular mechanisms of NAR efficiently loaded into cationic nanoparticles (NP-NAR) for treating metabolic dysfunction-associated steatotic liver disease (MASLD) in a mouse model. The results demonstrated that NP-NAR effectively ameliorated lipid metabolism dysbiosis, oxidative stress, insulin resistance, and inflammation in MASLD mice. Transcriptomic analysis and molecular data revealed that NP-NAR promoted fatty acid oxidation via activation of the PPAR signaling pathway, reduced hepatic lipid uptake and lipogenesis by inhibiting the expressions of key genes including CD36, ACC, and FASN. Moreover, NP-NAR modulated cholesterol metabolism by inhibiting the classical bile acid synthesis pathway. 16 S rDNA gene sequencing revealed a disbalanced gut microbiota in MASLD mice, whereas NP-NAR treatment statistically reversed the abundance changes of several intestinal bacteria at the phylum and genus levels, which partly contributed to the balance in intestinal metabolite production, including short-chain fatty acids. In conclusion, these findings suggest that NP-NAR may be a promising candidate for the treatment of obesity-associated MASLD, offering new insight into the mechanisms underlying NAR's efficacy against MASLD.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"168"},"PeriodicalIF":10.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557160","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":"Conditioning period impacts the morphology and proliferative effect of extracellular vesicles derived from rat adipose tissue derived stromal cell.","authors":"Anton Borger, Maximilian Haertinger, Flavia Millesi, Lorenz Semmler, Paul Supper, Sarah Stadlmayr, Anda Rad, Christine Radtke","doi":"10.1186/s12951-025-03273-6","DOIUrl":"10.1186/s12951-025-03273-6","url":null,"abstract":"<p><p>A serum-free conditioning period is a crucial step during small extracellular vesicle (sEV) preparation ranging from 12 to 72h. There is a paucity of knowledge about downstream effects of serum-free conditioning on sEVs and the optimal duration of the conditioning period. The aim of this study was to investigate the influence of the serum-free conditioning period on the sEVs derived from primary adipose stromal cells (AdSCs) and their regenerative potential. Primary AdSCs were conditioned in serum-free medium for 72h. Conditioned medium was collected and refreshed every 24h obtaining three fractions, namely sEVs released after 24h (early), 24h to 48h (intermediate) and 48h to 72h (late). After sEV enrichment with ultracentrifugation, the sEV fractions were analyzed by their size, phenotypic expression, and morphology. Proliferation assays of primary Schwann cells after treatment with sEVs were performed. Particles meeting criteria to be classified as sEVs were detected in all fractions. However, sEVs differed by their size and phenotypic expression. A long conditioning period led to a heterogenous population of larger sEVs and increased protein per particle ratio. Moreover, the expression of tetraspanines was affected. Lastly, the proliferative effect of sEVs on Schwann cells decreased with increasing conditioning period. In conclusion, particles meeting the criteria of EVs are released by primary AdSCs over 72h under serum free conditioning. Nonetheless, they significantly differ in their proliferative effect on Schwann cells cultures.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"164"},"PeriodicalIF":10.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542278","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":"Cascade-recharged macrophage-biomimetic ruthenium-based nanobattery for enhanced photodynamic-induced immunotherapy.","authors":"Guoyu Xia, Zhongxiong Fan, Qingluo Wang, Jianmin Li, Yuxiang Zhang, Adila Aipire, Qiurong Su, Ying Li, Zhenqing Hou, Jinyao Li","doi":"10.1186/s12951-025-03255-8","DOIUrl":"10.1186/s12951-025-03255-8","url":null,"abstract":"<p><p>Photodynamic-induced immunotherapy (PDI) is often hampered by low reactive oxygen species (ROS) yield, intra-tumor hypoxia, high glutathione (GSH) concentration, and immunosuppressive microenvironment. In view of this, a ruthenium (Ru)-based nanobattery (termed as IRD) with cascade-charged oxygen (O₂), ROS, and photodynamic-induced immunotherapy by coordination-driven self-assembly of transition-metal Ru, photosensitizer indocyanine green (ICG), and organic ligand dithiobispropionic acid (DTPA). Then, IRD is camouflaged with macrophage membranes to obtain a nanobattery (termed as IRD@M) with targeting and immune evasion capabilities. Upon intravenous administration, IRD@M with a core-shell structure, nano diameter, and good stability can specifically hoard in tumor location and internalize into tumor cells. Upon disassembly triggered by GSH, the released Ru³⁺ not only catalyzes the conversion of endogenous hydrogen peroxide (H₂O₂) into O₂ to alleviate tumor hypoxia and reduce the expression of hypoxia-inducible factor-1α (HIF-1α), but also generates hydroxyl radicals (·OH) to elevate intracellular ROS levels. This process significantly enhances the photodynamic therapy (PDT) efficacy of the released ICG. Meanwhile, the released DTPA can significantly downregulate overexpressed GSH to reduce the elimination of ROS deriving from PDT by the exchange reaction of thiol-disulfide bond. It is also found that alleviating the hypoxic tumor microenvironment synergistically enhances the PDT efficacy, which in turn cascades to recharge the subsequent immune response, significantly improving the immunosuppressive tumor microenvironment and activating systemic tumor-specific immunity. Notably, in vitro and in vivo experimental results jointly confirm that such cascade-recharged macrophage-biomimetic Ru-based nanobattery IRD@M can achieve an obvious tumor elimination while results in a minimized side effect. Taken together, this work highlights a promising strategy for simple, flexible, and effective Ru-based immunogenic cell death (ICD) agents within PDI.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"167"},"PeriodicalIF":10.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557158","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}