Photoinduced Synergism of Ferroptosis/Pyroptosis/Oncosis by an O2-Independent Photocatalyst for Enhanced Tumor Immunotherapy

IF 14.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of the American Chemical Society Pub Date : 2025-03-20 DOI:10.1021/jacs.4c17268

Shankun Yao, Fengwu Xu, Ying Wang, Jizhen Shang, Shumeng Li, Xinyu Xu, Zhipeng Liu, Weijiang He, Zijian Guo, Yuncong Chen

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引用次数: 0

Abstract

Due to O₂ dependence, hypoxia-induced apoptosis resistance, and immunosuppressive microenvironment, the effect of traditional photodynamic therapy toward hypoxic solid tumors is severely limited. Herein, we report an O₂-independent photocatalyst (EBSe) for tumor immunotherapy potentiation via synergism of near-infrared (NIR) light-induced ferroptosis/pyroptosis/oncosis. Simple Se and ethyl modifications on methylene blue (MB) endow EBSe with a remarkable phototoxicity enhancement (>2500 folds) and an excellent phototoxicity index (PI > 32,000) to 4T1 cells under hypoxia. EBSe exhibits self-adaptive photodynamic processes that generate enhanced type I/II ROS under normoxia and elevate carbon radical production under hypoxia. Interestingly, EBSe shows much higher cell uptake and undergoes photoinduced lysosomal-to-nucleus translocation, which activates ferroptosis, pyroptosis, and oncosis. The synergism of three nonapoptotic pathways potentiates antitumor immune responses in 4T1 tumor-bearing mice. This work offers a reliable strategy for developing powerful PSs to overcome the apoptosis resistance and immunosuppressive microenvironment of hypoxic tumors.

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来源期刊

Journal of the American Chemical Society 化学-化学综合

CiteScore

24.40

自引率

6.00%

发文量

2398

审稿时长

1.6 months

期刊介绍： The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.