{"title":"Harnessing the power of traceable system C-GAP: homologous-targeting to fire up T-cell immune responses with low-dose irradiation.","authors":"Weijie Zhuang, Kuangwu Pan, Jie Wu, Leyi Liu, Shiyu Lv, Jiajun Hu, Fangyang Shi, Wei Zhao, Dongsheng Yu","doi":"10.1186/s12951-025-03281-6","DOIUrl":null,"url":null,"abstract":"<p><p>While radiotherapy-induced immunogenic cell death (ICD) holds potential for enhancing cancer immunotherapy, the conventional high-dose irradiation often leads to an immunosuppressive microenvironment and systemic toxicity. Therefore, a biomimetic nanoplatform cell membrane coated-nitrogen-doped graphene quantum dots combined with Au nanoparticles (C-GAP) was developed in this study. Firstly, homologous and traceable targeting features of C-GAP enables tumor-selective accumulation, providing reference for the selection of the timing of radiotherapy. Secondly, radiosensitization by C-GAP with Low-dose irradiation (LDI) amplifies reactive oxygen species (ROS) generation to trigger potent ICD. Thirdly, remarkable immune remodeling induced by C-GAP enhances CD8<sup>+</sup> T cell infiltration and effector function. Single-cell RNA sequencing revealed that C-GAP-LDI combination upregulates TNF and CCL signaling pathway expression in tumor-infiltrating CD8<sup>+</sup> T cells which potentiates tumor eradication. Our findings present a novel approach for safe and effective radioimmunotherapy, where C-GAP sensitized LDI achieves therapeutic enhancement through precise ICD induction and systemic immune activation.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"207"},"PeriodicalIF":10.6000,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905511/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nanobiotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1186/s12951-025-03281-6","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
While radiotherapy-induced immunogenic cell death (ICD) holds potential for enhancing cancer immunotherapy, the conventional high-dose irradiation often leads to an immunosuppressive microenvironment and systemic toxicity. Therefore, a biomimetic nanoplatform cell membrane coated-nitrogen-doped graphene quantum dots combined with Au nanoparticles (C-GAP) was developed in this study. Firstly, homologous and traceable targeting features of C-GAP enables tumor-selective accumulation, providing reference for the selection of the timing of radiotherapy. Secondly, radiosensitization by C-GAP with Low-dose irradiation (LDI) amplifies reactive oxygen species (ROS) generation to trigger potent ICD. Thirdly, remarkable immune remodeling induced by C-GAP enhances CD8+ T cell infiltration and effector function. Single-cell RNA sequencing revealed that C-GAP-LDI combination upregulates TNF and CCL signaling pathway expression in tumor-infiltrating CD8+ T cells which potentiates tumor eradication. Our findings present a novel approach for safe and effective radioimmunotherapy, where C-GAP sensitized LDI achieves therapeutic enhancement through precise ICD induction and systemic immune activation.
期刊介绍:
Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.