Remote Manipulation of ROS-Sensitive Calcium Channel Using Near-Infrared-Responsive Conjugated Oligomer Nanoparticles for Enhanced Tumor Therapy <i>In Vivo</i>.

Abstract

The regulation of reactive oxygen species (ROS)-sensitive calcium (Ca²⁺) channels is of great significance in the treatment of tumors. Here, a simple ROS generation system is developed to activate ROS-sensitive ion channels for enhancing calcium-cascade-mediated tumor cell death under near-infrared (NIR) light irradiation. Upon irradiation with an 808 nm laser, a low-lethality amount of ROS facilitates plasmid transient potential receptor melastatin-2 (pTRPM2) gene release via cleavage of the Se-Se bonds, which contributed to enhancing the expression of TRPM2 in tumor cells. Meanwhile, ROS could potently activate TRPM2 for Ca²⁺ influx to inhibit early autophagy and to further induce intracellular ROS production, which ultimately led to cell death in TRPM2 expressing tumor cells. Both <i>in vitro</i> and <i>in vivo</i> data show that nanoparticles have an excellent therapeutic effect on cancer upon NIR light. This work presents a simple modality based on NIR light to remotely control the ROS-sensitive ion channel for cancer therapy.