Hao Liang, Ling Yu-Yi, Wang Jie, Shen Qing-Hua, Li Zhi-Yuan, Tan Cai-Ping
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510006, P. R. China.
The Marine Biomedical Research Institute of Guangdong Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, Guangdong 524023, P. R. China.
J Med Chem. 2025 Jan 9;68(1):338-347. doi: 10.1021/acs.jmedchem.4c01948. Epub 2024 Dec 25.
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 () 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 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.
内质网自噬在癌症的发生、发展和治疗中是一把双刃剑；特别是，其在免疫治疗中的作用仍不清楚。在这项工作中，我们设计了一种含有硼二吡咯衍生配体和β-咔啉配体的诊疗用铼配合物（），以靶向内质网并在后期阻断内质网自噬。有趣的是，正如在体外和体内所验证的那样，内质网自噬阻断大大增强了诱导免疫原性细胞死亡（ICD）的能力。总之，我们巧妙地将两个用于内质网靶向和内质网自噬阻断的分子模块融合到一个配位化合物中，以提供一种高效的ICD诱导剂，这为设计新的癌症免疫疗法提供了线索。
