Light-Induced Reactive Oxygen Species (ROS) Generator for Tumor Therapy through an ROS Burst in Mitochondria and AKT-Inactivation-Induced Apoptosis

Abstract

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 mitochondrialtargeted ROS-associated therapy hold great potential in cancer therapy.

A triphenylphosphine coordinated cinnamaldehyde-derived copper(i) Fenton-like agent with mitochondrial aggregation damage for chemodynamic therapy

“…Moreover, the decrease in the mitochondrial membrane potential also activated the expression of caspase family proteins. 43 Among them, caspase 3/9 plays a crucial role in the regulation and activation of cell apoptosis involving the mitochondria-mediated oxidative stress. 44 Subsequently, the ability of Cin-OD-Cu to activate caspase-3 and caspase-9 in A2780 cells was assessed by flow cytometry.…”

Hawthorn with “homology of medicine and food”: a review of anticancer effects and mechanisms

“…It is mainly manifested in the induction of ROS production after drug treatment. The significant accumulation of ROS disrupts the integrity and function of mitochondria, ultimately activating caspase-3 or caspase-9 and initiating apoptosis ( Tu et al, 2021 ). Additionally, ROS production triggers endoplasmic reticulum stress, which results in the accumulation of Ca 2+ and the induction of apoptosis in cancer cells.…”

Application and prospect of ROS-related nanomaterials for orthopaedic related diseases treatment

“…As mentioned above, the production of ROS in cells or microenvironment increases significantly under significant stress, and endogenous antioxidants cannot remove all ROS, resulting in serious damage to biomolecules including DNA, lipids and proteins, and triggering a series of reactions such as ER stress and mitochondrial damage related apoptosis ( Tian et al, 2020 ; Tu et al, 2021 ). This is an important mechanism by which ROS promotes the occurrence and development of orthopaedic diseases.…”