Theranostic Rhenium(I)-Based ER-Phagy Retardant Promotes Immunogenic Cell Death

ER-phagy is a double-edged sword in the occurrence, development, and treatment of cancer; especially, its functions in immunotherapy are still unknown. In this work, we designed a theranostic Re complex (Re1) containing a BODIPY-derived ligand and a β-carboline ligand to target the endoplasmic reticulum (ER) and block ER-phagy at the late stages. Interestingly, as validated both in vitro and in vivo, ER-phagy blockage greatly enhances the capability of Re1 to induce immunogenic cell death (ICD). In summary, we dexterously fused two molecular modules for ER targeting and ER-phagy blockage into a coordination complex to afford a highly effective ICD inducer, which provides clues for designing new cancer immunotherapeutics.内质网自噬（ER-phagy）在癌症的发生、发展与治疗过程中堪称一把双刃剑，其在免疫治疗中的具体作用机制至今仍未明晰。本研究设计了一种诊疗一体化铼配合物（Re1），该配合物包含氟化硼二吡咯（BODIPY）衍生配体与β-咔啉配体，能够靶向内质网（ER）并阻断晚期阶段的内质网自噬。值得注意的是，经体外与体内实验验证，内质网自噬的阻断可显著增强Re1诱导免疫原性细胞死亡（ICD）的能力。综上，本研究巧妙地将内质网靶向与内质网自噬阻断这两个分子模块整合至配位化合物中，得到了一种高效的免疫原性细胞死亡诱导剂，为新型癌症免疫治疗药物的研发提供了重要线索。