Ling Yu-Yi, Wang Wen-Jin, Hao Liang, Wu Xiao-Wen, Liang Jing-Hao, Zhang Hang, Mao Zong-Wan, Tan Cai-Ping
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, State Key Laboratory of Oncology in South China, Sun Yat-Sen University, Guangzhou, 510006, P. R. China.
Small. 2022 Dec;18(49):e2203659. doi: 10.1002/smll.202203659. Epub 2022 Oct 30.
Photoimmunotherapy is attractive for cancer treatment due to its spatial controllability and sustained responses. This work presents a ferrocene-containing Ir(III) photosensitizer (IrFc1) that can bind with transferrin and be transported into triple-negative breast cancer (TNBC) cells via a transferrin receptor-mediated pathway. When the ferrocene in IrFc1 is oxidized by reactive oxygen species, its capability to photosensitize both type I (electron transfer) and type II (energy transfer) pathways is activated through a self-amplifying process. Upon irradiation, IrFc1 induces the generation of lipid oxidation to cause ferroptosis in TNBC cells, which promotes immunogenic cell death (ICD) under both normoxia and hypoxia. In vivo, IrFc1 treatment elicits a CD8 T-cell response, which activates ICD in TNBC resulting in enhanced anticancer immunity. In summary, this work reports a small molecule-based photosensitizer with enhanced cancer immunotherapeutic properties by eliciting ferroptosis through a self-amplifying process.
光免疫疗法因其空间可控性和持续反应而在癌症治疗中颇具吸引力。这项工作展示了一种含二茂铁的铱（III）光敏剂（IrFc1），它可以与转铁蛋白结合，并通过转铁蛋白受体介导的途径转运到三阴性乳腺癌（TNBC）细胞中。当IrFc1中的二茂铁被活性氧氧化时，其对I型（电子转移）和II型（能量转移）途径的光敏能力会通过一个自我放大过程被激活。照射后，IrFc1诱导脂质氧化的产生，从而在TNBC细胞中引发铁死亡，这在常氧和缺氧条件下均促进免疫原性细胞死亡（ICD）。在体内，IrFc1治疗引发CD8 T细胞反应，激活TNBC中的ICD，从而增强抗癌免疫力。总之，这项工作报道了一种基于小分子的光敏剂，通过自我放大过程引发铁死亡，具有增强的癌症免疫治疗特性。
