文献类型：期刊文献

英文题名：Ferroptosis and Pyroptosis Co-Activated Nanomodulator for "Cold" Tumor Immunotherapy and Lung Metastasis Inhibition

作者：Jiang, Cong[1];Li, Xianglong[2];Pan, Fen[3];Zhang, Lele[1];Yu, Huansha[1];Zhang, Jing[1];Zou, Jinglin[2];Zhong, Tianyu[2];Zhang, Dapeng[2];Yang, Yang[1];Li, Yongsheng[2];Zhang, Peng[1]

机构：[1]Tongji Univ, Shanghai Pulm Hosp, Dept Thorac Surg, Sch Med, Shanghai 200092, Peoples R China;[2]East China Univ Sci & Technol, Frontier Sci Ctr Mat Biol & Dynam Chem, Shanghai Engn Res Ctr Hierarch Nanomat, Sch Mat Sci & Engn,Lab Low Dimens Mat Chem,Key Lab, Shanghai 200237, Peoples R China;[3]Shanghai Jiao Tong Univ, Shanghai Childrens Hosp, Sch Med, Dept Clin Lab, Shanghai 200062, Peoples R China

年份：2023

卷号：33

期号：37

外文期刊名：ADVANCED FUNCTIONAL MATERIALS

收录：;EI(收录号：20232214155702);WOS:【SCI-EXPANDED(收录号:WOS:000995175100001)】；

基金：C.J., X.L., and F.P. contributed equally to this work. This work was financially supported by the National Natural Science Foundation of China (no. 81972172, 51621002, and 51972112), Shanghai Municipal Science and Technology Major Project (grant no. 2018SHZDZX03), Basic Research Program of Shanghai (21JC1406003 and 19JC1411700), Leading Talents in Shanghai in 2018, the 111 project (B14018), Clinical Research Plan of SHDC (grant no. SHDC2020CR2020B), and Funding of Shanghai Pulmonary Hospital (grant no. FKCX1904 and no. FKLY20004). All experiments on animals were operated in terms of the protocols approved by the Laboratory Animal Management Committee of East China University of Science and Technology (license 5 number: ECUST-2020-04001).

语种：英文

外文关键词：anti-PD-L1; ferroptosis; immunosuppressive tumor microenvironment; immunotherapy; pyroptosis

摘要：Immune checkpoint blockade (ICB) therapy is an emerging strategy for cancer immunotherapy; however, the actual effects of ICB therapy are greatly limited by the immunosuppressive tumor microenvironment (TME, i.e., "cold" tumors). Although engineered nanomaterials display significant importance to regulate TME in cancer treatment, most of them focus on "immunosilent" apoptotic processes that cannot elicit sufficient immune responses for further immunotherapy. Herein, a GSH-responsive nanomodulator is reported that can reverse the immunosuppressive TME for "cold" tumor immunotherapy and lung metastasis inhibition through simultaneous ferroptosis and pyroptosis induction. The nanomodulator is constructed by loading FDA-approved sulfasalazine (SAS) and doxorubicin (DOX) on disulfide-doped organosilica hybrid micelles, where SAS and DOX are released through the GSH-stimulated rupture of micelles to induce ferroptosis and pyroptosis, respectively, promoting dendritic cells (DCs) maturation and cytotoxic T lymphocytes (CTLs) elevation through massive tumor-associated antigen release. In vivo experimental results verify that desirable tumor destruction of the nanomodulator at low concentrations is achieved. More importantly, combination of this nanomodulator and programed death ligand-1 antibodies significantly inhibits primary tumors and distant lung metastases as a result of elevated mature DCs and CTLs. This strategy to modulate immunosuppressive TME by nanomodulator-induced non-apoptotic death provides a new promising paradigm for ICB therapy.