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

J Med Chem. 2024 Dec 25. doi: 10.1021/acs.jmedchem.4c01948. Online ahead of print.

Abstract

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.