不依赖于o2的光催化剂在增强肿瘤免疫治疗中的光诱导增效作用

IF 15.6 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

摘要

由于氧依赖、缺氧诱导的细胞凋亡抵抗和免疫抑制微环境，传统光动力治疗对缺氧实体瘤的效果严重受限。在此，我们报道了一种不依赖于o2的光催化剂（EBSe），通过近红外（NIR）光诱导的铁坏死/焦亡/肿瘤的协同作用，增强了肿瘤免疫治疗。在亚甲基蓝（MB）上进行简单的Se和乙基修饰，使EBSe具有显著的光毒性增强（约2500倍）和良好的光毒性指数（PI）。32,000)至4T1细胞缺氧。EBSe表现出自适应光动力过程，在常氧条件下产生增强的I/II型ROS，在缺氧条件下提高碳自由基的产生。有趣的是，EBSe表现出更高的细胞摄取，并经历光诱导溶酶体到细胞核的易位，从而激活铁下垂、焦下垂和肿瘤。三种非凋亡通路的协同作用增强了4T1荷瘤小鼠的抗肿瘤免疫反应。这项工作为开发强大的PSs来克服缺氧肿瘤的细胞凋亡抵抗和免疫抑制微环境提供了可靠的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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

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

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.