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Molecular Rotor-Based NIR-II TICTgens for Mitochondria-Targeted Pyroptosis Induction and Multi-Model Monitoring of Cancer Immunotherapy

文献类型：期刊论文

作者Li, Min7,8; Gao, Jing5,6; Xie, Yaxiong4,5,6; Zhu, Zifan7; Huang, Lujia4,5,6; Lai, Yi5,6; Yar, Muhammad3,5,6; Bajda, Marek2; Li, Ming8; Yu, Haijun4,5,6
刊名ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
出版日期2025-07-29
页码14
关键词Cancer immunotherapy Multi-modal imaging Pyroptosis Twisted intramolecular charge transfer luminogens Viscosity
DOI10.1002/anie.202508646
通讯作者Wang, Feng(prof.fengwang@tongji.edu.cn) ; Xu, Zhiai(zaxu@chem.ecnu.edu.cn)
英文摘要Pyroptosis has emerged as a promising mechanism for eliciting robust antitumor immunity; however, the current pyroptosis inducers lack tumor-selectivity and feedback of therapeutic effect. In this study, we developed a series of twisted intramolecular charge transfer luminogens (TICTgens) for precisely regulating and in situ monitoring of tumor cell pyroptosis in vitro and in vivo. The outperformed TICTgen HCM displayed second near-infrared (NIR-II) fluorescence emission and exceptional viscosity sensitivity. Upon 671 nm laser irradiation, HCM induced the generation of type-I/II reactive oxygen species (ROS) and hyperthermia effect, which cumulatively triggered mitochondrial damage and pyroptosis of tumor cells. HCM was systemically delivered via intracellular acidity-sensitive nanoparticles (namely PDPA@HCM NPs) to effectively trigger pyroptosis-driven antitumor immunity. Notably, HCM performed NIR-II fluorescence and photoacoustic (PA) imaging of pyroptosis-induced mitochondrial dysfunction by measuring viscosity change, thus enabling in situ monitoring of pyroptosis-mediated antitumor immunotherapy. In combination with immune checkpoint blockade therapy, the PDPA@HCM NPs dramatically regressed colorectal tumor growth in a mouse model. Overall, this study demonstrated that the TICTgens could serve as a versatile platform for pyroptosis induction and monitoring of pyroptosis-based cancer immunotherapy.
WOS关键词CELL-DEATH ; CLEAVAGE
资助项目National Natural Science Foundation of China ; Science and Technology Commission of Shanghai Municipality[23490712700] ; Shanghai Academic/Technology Research Leader[23XD1433000] ; Shanghai Oriental Talents Program[BJKJ2024046] ; Shanghai Oriental Talents Program[BJWS2024032] ; Shanghai Advanced Research Institute, CAS ; Shanghai Institute of Materia Medica, CAS ; [22474042] ; [U22A20328] ; [W2412035]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001540300400001
出版者WILEY-V C H VERLAG GMBH
源URL[http://119.78.100.183/handle/2S10ELR8/321177]  
专题中国科学院上海药物研究所
通讯作者Wang, Feng; Xu, Zhiai
作者单位1.Fudan Univ, Huadong Hosp, Dept Gastroenterol, Shanghai 200040, Peoples R China
2.Jagiellonian Univ Med Coll, Fac Pharm, Dept Physicochem Drug Anal, PL-30688 Krakow, Poland
3.COMSATS Univ Islamabad, Interdisciplinary Res Ctr Biomed Mat, Lahore 54000, Pakistan
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
7.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China
8.Fudan Univ, Huadong Hosp, Dept Radiol, Shanghai 200040, Peoples R China
推荐引用方式
GB/T 7714		 Li, Min,Gao, Jing,Xie, Yaxiong,et al. Molecular Rotor-Based NIR-II TICTgens for Mitochondria-Targeted Pyroptosis Induction and Multi-Model Monitoring of Cancer Immunotherapy[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2025:14.
APA Li, Min.,Gao, Jing.,Xie, Yaxiong.,Zhu, Zifan.,Huang, Lujia.,...&Xu, Zhiai.(2025).Molecular Rotor-Based NIR-II TICTgens for Mitochondria-Targeted Pyroptosis Induction and Multi-Model Monitoring of Cancer Immunotherapy.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,14.
MLA Li, Min,et al."Molecular Rotor-Based NIR-II TICTgens for Mitochondria-Targeted Pyroptosis Induction and Multi-Model Monitoring of Cancer Immunotherapy".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2025):14.

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来源：上海药物研究所

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