Light-Induced Reactive Oxygen Species(ROS) Generator For Tumor Therapy Through An ROS Burst In Mitochondria And AKTInactivation-Induced Apoptosis

The incidence rate of breast cancer is the highest among all the kinds of tumor in the world,and it is a great threat to women’s physical and mental health.The incidence rate of breast cancer has replaced lung cancer and became the world’s largest cancer.In terms of cancer related mortality,the mortality rate of breast cancer is also high.The incidence rate of breast cancer in China has been increasing year by year in the past decades.The incidence rate of breast cancer is the top of the list for Chinese women.The main treatments for breast cancer include surgery,chemotherapy,radiotherapy,endocrine therapy,targeted therapy and immunotherapy.Photodynamic therapy has become an important method for local treatment of breast cancer in recent years.The principle of photodynamic therapy for tumor is to make photosensitizer react and induce cell apoptosis under the induction of specific light.Mitochondria mediated apoptosis is one of the important pathways of apoptosis.External stimuli will induce the burst of reactive oxygen species in mitochondria,causing a series of biological changes in mitochondria and finally lead to mitochondria mediated apoptosis.This will lead to the release of cytochrome c to the cytoplasm,activate its downstream target caspase-9 and form an apoptotic complex.The complex will further activate caspase-3,the key enzyme of apoptosis,and trigger the apoptosis cascade.We intend to develop a new type of active oxygen photosensitizer named a light-induced ROS generator(TBTP).TBTP can induce oxygen burst in mitochondria and stimulate apoptosis mediated by mitochondrial pathway both in vitro and in vivo.Reactive oxygen species(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.ROS burst in mitochondria can kill tumor cells via inhibition of the AKT pathway.TBTP serves as an effifficient ROS generator with low cytotoxicity,favorable biocompatibility,excellent photostability,mitochondria-targeted properties.Taken together,TBTP has a good prospect of clinical application attributes to its characteristics of high efficiency in inducing cancer cell apoptosis,high stability and low toxicity.