A pH/light dual-responsive nanoprodrug to release nitric oxide and ROS for Cascade photodynamic therapy

Photodynamic therapy (PDT) could induce apoptosis by releasing reactive oxygen species (ROS) to treat tumor. Application of pH/light dual-activated nanoparticles could generate ROS in the acidic tumor microenvironment under 808 nm laser irradiation for precise treatment. L-arginine (L-Arg) triggered by ROS is an efficient nitric oxide (NO) donor for gas therapy. In addition, it is reported that peroxynitrite (ONOO-) produced by rapid reaction of ROS and NO could sensitize PDT and induce apoptosis for synergistic treatment. Herein, we developed the L-Arg loaded pH/light dual-activated PEGylated photosensitizer for self-assembly into nanoparticles named Rho-Arg. As measured by fluorescence spectroscopy, the pKa of Rho-Arg was 5.5, which is suitable for applying in the tumor microenvironment. The nanoplatform was firstly activated under the acidic condition of tumor, and then illuminated by 808 nm laser to controllably release ROS, and sequentially produced NO and ONOO-. In conclusion, the Rho-Arg nanoplatform may provide a promising synergistic therapy tool for tumor treatment.