ROS-induced NO generation for gas therapy and sensitizing photodynamic therapy of tumor

Abstract This study reports a tumor-specific ROS-responsive nanoplatform capable of the combination of nitric oxide (NO)-based gas therapy and sensitized photodynamic therapy (PDT). The nanoplatform is constructed on porous coordination network (PCN), which contains NO donor L-Arg and is concurrently coated with cancer cell membrane (L-Arg@PCN@Mem). Under near infrared light (NIR) irradiation, L-Arg@PCN@Mem produces plenty of reactive oxygen species (ROS) directly for PDT therapy, while a part of ROS take the role of oxidative to converse L-Arg into NO for combined gas therapy. The results indicate that the transformation of ROS to NO can enhance PDT efficacy in hypoxic tumors owing to the ability of NO in freely diffusing into deep hypoxic tumor site. Moreover, homologous targeting function originated from the coating of cancer cells membrane further improves the tumor treatment effect owing to the biotargeting toward homologous tumors. This L-Arg@PCN@Mem nanoplatform provides a new therapy paradigm of overcoming the hypoxia barrier of tumor therapy, and holds great potential for the treatment of tumor and NO-related diseases.