Boosting Reactive Oxygen Species Generation with a Dual-Catalytic Nanomedicine for Enhanced Tumor Nanocatalytic Therapy
Guoting Su, Hui Xu, Fangfang Zhou, Xiyu Gong, Songwen Tan, Yongju He
Abstract
Generating lethal reactive oxygen species (ROS) within tumors by nanocatalytic medicines is an advanced strategy for tumor-specific therapy in recent years. Nevertheless, the low yield of ROS restrains its therapeutic efficiency. Herein, a dual-catalytic nanomedicine based on tumor microenvironment (TME)-responsive liposomal nanosystem co-delivering CuO 2 and dihydroartemisinin (DHA) (LIPSe@CuO 2 &DHA) is developed to boost ROS generation against tumor. The liposomal nanosystem can degrade in the ROS-overexpressed TME and liberate CuO 2 and DHA to initiate Cu-based dual-catalytic ROS generation. Serving as generators of H 2 O 2 and Cu 2+, CuO 2 can self-produce plenty of toxic hydroxyl radicals via Fenton-like reaction in the acidic TME. Meanwhile, the released Cu 2+ can catalyze DHA to generate cytotoxic C-centered radicals. Together, the self-supplied H 2 O 2 and Cu-based dual-catalytic reaction greatly increase the intratumoral level of lethal ROS. Importantly, Cu 2+ can decrease the GSH-mediated scavenging effect on the produced ROS via a redox reaction and undergo a Cu 2+ -to-Cu + conversion to enhance the Fenton-like reaction, further guaranteeing the high efficiency of ROS generation. Resultantly, LIPSe@CuO 2 &DHA induces remarkable cancer cell death and tumor growth inhibition, which may present a promising nanocatalytic medicine for cancer therapy.