Simultaneous Light-Triggered Release of Nitric Oxide and Carbon Monoxide from a Lipid-Coated Upconversion Nanosystem Inhibits Colon Tumor Growth
Yaw Opoku‐Damoah, Run Zhang, Hang T. Ta, Zhi Ping Xu
Abstract
Gas therapy has gained noteworthy attention in biomedical research, with the rise of gas-releasing molecules enhancing their therapeutic potential, especially when integrated into nano-based drug delivery systems. Herein, we present a lipid-coated gas delivery system to simultaneously shuttle two gas-releasing molecules carrying nitric oxide (NO) and carbon monoxide (CO), respectively. Upconversion nanoparticles (UCNPs) are designed to generate photons at 360 nm upon 808 nm of near-infrared (NIR) irradiation. These in situ-generated UV photons trigger simultaneous NO and CO release from S -nitrosoglutathione (GSNO) and the CO-releasing molecule (CORM), respectively, which are coloaded into lipid-coated UCNP/GSNO/CORM/FA nanoparticles (LUGCF). LUGCF with a GSNO/CORM mass ratio of 2:1 is determined to be optimal in terms of synergistically instigating apoptosis in HCT116 and CT26 colon cancer cells, where both NO/CO are released and subsequent production of ROS are detected. This CO/NO combination nanoplatform exhibits a very effective inhibition of colon tumor growth in vivo at relatively low doses upon a mild 808 nm irradiation. Overall, we effectively integrated two therapeutic gas-releasing molecules in one NIR-responsive nanosystem, presenting a promising therapeutic strategy for future biomedical applications in dual-gas cancer therapy.