Light-Induced Reactive Oxygen Species (ROS) Generator for Tumor Therapy through an ROS Burst in Mitochondria and AKT-Inactivation-Induced Apoptosis
Mitochondria are identified as a valuable target for cancer therapy owing to their primary function in energy supply and cellular signal regulation. Mitochondria in tumor cells are depicted by excess reactive oxygen species (ROS), which lead to numerous detrimental results. Hence, mitochondria-targeting ROS-associated therapy is an optional therapeutic strategy for cancer. In this contribution, a light-induced ROS generator (TBTP) is developed for evaluation of the efficacy of mitochondria-targeting ROS-associated therapy and investigation of the mechanism underlying mitochondrial-injure-mediated therapy of tumors. TBTP serves as an efficient ROS generator with low cytotoxicity, favorable biocompatibility, excellent photostability, mitochondria-targeted properties, and NIR emission. In vivo and in vitro experiments reveal that TBTP exhibits effective anticancer potential. ROS generated from TBTP could destroy the integrity of mitochondria, downregulate ATP, decrease the mitochondrial membrane potential, secrete Cyt-c into cytoplasm, activate Caspase-3/9, and induce cell apoptosis. Moreover, RNA-seq analysis highlights that an ROS burst in mitochondria can kill tumor cells via inhibition of the AKT pathway. All these results prove that mitochondrial-targeted ROS-associated therapy hold great potential in cancer therapy.
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