Potent Zinc(II)-Based Immunogenic Cell Death Inducer Triggered by ROS-Mediated ERS and Mitochondrial Ca 2+ Overload.

and are Zn-based complexes that activate the immunogenic cell death (ICD) effect by Ca-mediated endoplasmic reticulum stress (ERS) and mitochondrial dysfunction. Compared with , effectively caused reactive oxidative species (ROS) overproduction in the early phase, leading to ERS response. Severe ERS caused the release of Ca from ER to cytoplasm and further to mitochondria. Excessive Ca in mitochondria triggered mitochondrial dysfunction. The damage-associated molecular patterns (DAMPs) of CRT, HMGB1, and ATP occurred in T-24 cells exposed to and . The vaccination assay demonstrated that and efficiently suppressed the growth of distant tumors. The elevated CD8 cytotoxic T cells and decreased Foxp3 cells in vaccinated mice supported our conclusion. Moreover, and improved the survival rate of mice compared with oxaliplatin. Collectively, our findings provided a new design strategy for a zinc-based ICD inducer via ROS-induced ERS and mitochondrial Ca overload.