Reactive Oxygen Species-Enhanced Low-Dose Chemo-Photodynamic Therapy for Gastric Cancer

Abstract

A photosensitizer can react with oxygen or a substrate based on energy or electron transfer processes in order to generate free radicals, singlet oxygen (SOG), or other reactive oxygen species (ROS). SOG can damage cellular components and eventually cause cell death. However, SOG generation requires sufficient oxygen. Therefore, the effect of photodynamic therapy (PDT) via SOG may be decreased in oxygen-deficient tumor tissues, including gastric cancer. Here, we synthesized a nanosized cationic liposome integrated with a photosensitizer and low-dose chemotherapeutic drug related to ROS to improve the ROS-mediated PDT effect and lower the risk of drug resistance and side effects induced by chemotherapy. The cationic liposome was used as a drug carrier to increase the efficiency of drug delivery, prolong drug circulation time, and achieve the simultaneous delivery of the photosensitizer and chemotherapeutic drug. The low-dose chemotherapeutic agent related to ROS was adopted for increasing the permeability of the mitochondrial membrane and inducing the entry of high levels of the photosensitizer into the cell so as to generate toxic ROS. Generally, the ROS-mediated enhanced effect could quickly induce long-lasting apoptosis. This integrated nanosized cationic liposome system is a potential agent for gastric cancer therapy and is based on enhanced ROS-mediated synergistic therapy.