文献类型：期刊文献

英文题名：A Carbon-Caged Rhodamine Generating Nitrosoperoxycarbonate for Photoimmunotherapy

作者：Yin, Lei[1];Zhao, Bei[3];Zhou, Jie[4];Huang, Yunxia[1];Ma, Hao[5];Zhou, Ting[6];Mou, Jie[6];Min, Peiru[5];Chen, Jinquan[4];Ge, Guangbo[3];Qian, Xuhong[1,2];Luo, Xiao[2];Yang, Youjun[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug Dev, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China;[3]Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai Frontiers Sci Ctr TCM Chem Biol, Shanghai 201203, Peoples R China;[4]East China Normal Univ, State Key Lab Precis Spect, Shanghai 200241, Peoples R China;[5]Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg, Sch Med, Shanghai 200011, Peoples R China;[6]Xuzhou Med Univ, Jiangsu Key Lab New drug & Clin Pharm, Xuzhou 221004, Jiangsu, Peoples R China

年份：2024

卷号：63

期号：26

外文期刊名：ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

收录：;EI(收录号：20242216172492);WOS:【SCI-EXPANDED(收录号:WOS:001230284200001)】；

基金：This work was supported by the National Key Research and Development Program of China (no. 2022YFD17800), the National Natural Science Foundation of China (nos. 22078098, 22278138, 81922070, 81973286, 82273897, 82372527, and 92156024), the Fundamental Research Funds for the Central Universities, the Shanghai Sailing Program (23YF1442700), the Shanghai Academic/Technology Research Leader (22XD1421000), the Research Funds of Happiness Flower ECNU (2020JK2103), the Open Funding Project of the State Key Laboratory of Bioreactor Engineering, and the State Key Laboratory of Fine Chemicals (KF2202).

语种：英文

外文关键词：Nitrosoperoxycarbonate; Immunogenic Cancer Therapy; Photo-trigger; Fluorescence-calibration

摘要：Photoimmunotherapy is a promising cancer treatment modality. While potent 1-e- oxidative species are known to induce immunogenic cell death (ICD), they are also associated with unspecific oxidation and collateral tissue damage. This difficulty may be addressed by post-generation radical reinforcement. Namely, non-oxidative radicals are first generated and subsequently activated into powerful oxidative radicals to induce ICD. Here, we developed a photo-triggered molecular donor (NPCD565) of nitrosoperoxycarbonate (ONOOCO2-), the first of its class to our knowledge, and further evaluated its feasibility for immunotherapy. Upon irradiation of NPCD565 by light within a broad spectral region from ultraviolet to red, ONOOCO2- is released along with a bright rhodamine dye (RD565), whose fluorescence is a reliable and convenient build-in reporter for the localization, kinetics, and dose of ONOOCO2- generation. Upon photolysis of NPCD565 in 4T1 cells, damage-associated molecular patterns (DAMPs) indicative of ICD were observed and confirmed to exhibit immunogenicity by induced maturation of dendritic cells. In vivo studies with a bilateral tumor-bearing mouse model showcased the potent tumor-killing capability of NPCD565 of the primary tumors and growth suppression of the distant tumors. This work unveils the potent immunogenicity of ONOOCO2-, and its donor (NPCD565) has broad potential for photo-immunotherapy of cancer. The first and visible light-triggered ONOOCO2- donor (NPCD565) was devised. Its photolysis generated a rhodamine dye along with two mild radicals, e.g., NO and CO2 & sdot;-. Their further combination with O2 yields ONOOCO2-, homolysis of which yields two potent radicals NO2 and CO3 & sdot;-, which were harnessed to induce immunogenic cell death of cancer cells. In mouse models, ablation of the primary tumor and suppression of the distant tumor were achieved. image