理想的肿瘤治疗策略涉及能够增强肿瘤微环境的免疫原性同时消除原发肿瘤的治疗方法。据报道，一种胆酸修饰的铱 (III) (Ir3) 光敏剂针对内质网 (ER)，对三阴性乳腺癌表现出有效的 I 型和 II 型光动力治疗作用 (MDA-MB-231) 。这种光敏剂通过光动力手段诱导由gasdermin E (GSDME) 介导的焦亡细胞死亡，并增强肿瘤免疫治疗。机制研究表明，复杂的 Ir3 在光照条件下会诱导 MDA-MB-231 乳腺癌细胞出现损伤相关分子模式 (DAMP) 特征。这些包括细胞表面钙网蛋白 (CRT) 外翻、细胞外高迁移率族蛋白 1 (HMGB1) 和 ATP 释放，并伴有 ER 应激和活性氧 (ROS) 增加。因此，复合物Ir3在光照条件下促进树突状细胞成熟和抗原呈递，充分激活体内T细胞依赖性免疫反应，最终在破坏原发肿瘤的同时消除远处肿瘤。总之，金属配合物介导的免疫调节和靶向干预代表了一种新的、有前途的肿瘤治疗方法。这为联合靶向治疗和免疫治疗的发展提供了有效的策略。版权所有 © 2024 Elsevier Inc. 保留所有权利。

An ideal tumor treatment strategy involves therapeutic approaches that can enhance the immunogenicity of the tumor microenvironment while simultaneously eliminating the primary tumor. A cholic acid-modified iridium(III) (Ir3) photosensitizer, targeted to the endoplasmic reticulum (ER), has been reported to exhibit potent type I and type II photodynamic therapeutic effects against triple-negative breast cancer (MDA-MB-231). This photosensitizer induces pyroptotic cell death mediated by gasdermin E (GSDME) through photodynamic means and enhances tumor immunotherapy. Mechanistic studies have revealed that complex Ir3 induces characteristics of damage-related molecular patterns (DAMPs) in MDA-MB-231 breast cancer cells under light conditions. These include cell-surface calreticulin (CRT) eversion, extracellular high mobility group box 1 (HMGB1) and ATP release, accompanied by ER stress and increased reactive oxygen species (ROS). Consequently, complex Ir3 promotes dendritic cell maturation and antigen presentation under light conditions, fully activates T cell-dependent immune response in vivo, and ultimately eliminates distant tumors while destroying primary tumors. In conclusion, immune regulation and targeted intervention mediated by metal complexes represent a new and promising approach to tumor therapy. This provides an effective strategy for the development of combined targeted therapy and immunotherapy.Copyright © 2024 Elsevier Inc. All rights reserved.