ROS-Responsive Nanoparticle Delivery of mRNA and Photosensitizer for Combinatorial Cancer Therapy

Messenger RNA (mRNA) therapy has shown tremendous potential for different diseases including cancer. While mRNA has been extensively used in cancer vaccine development as antigen or in cancer immunotherapy as immunomodulatory agent, the combination of mRNA therapy with photodynamic therapy has not been explored in cancer treatment. Herein, we report a reactive oxygen species (ROS)responsive polymeric nanoparticle (NP) platform for first-in-field codelivery of mRNA and photosensitizer for effective cancer treatment. We developed ROS-responsive oligomer-based polymeric NPs and applied them to test a combination of p53 mRNA and indocyanine green (ICG). The ROS-triggered disassembly of the NPs could promote mRNA translation efficiency, whereby p53 expression induced apoptosis of lung tumor cells. Meanwhile, the released ICG could lead to generation of ROS under 808 nm laser irradiation to induce photodynamic therapy. The NP codelivery of p53 mRNA and ICG demonstrated an effective and safe anti-tumor effect in a lung cancer model.

Automated summary

This study reports a reactive oxygen species (ROS)-responsive polymeric nanoparticle (NP) platform for the first time, enabling co-delivery of mRNA and a photosensitizer for effective cancer treatment. The ROS-triggered disassembly of the NPs promoted mRNA translation efficiency, leading to p53 expression-induced apoptosis of lung tumor cells. Meanwhile, the released photosensitizer induced photodynamic therapy under 808 nm laser irradiation. The co-delivery of mRNA and the photosensitizer demonstrated an effective and safe anti-tumor effect in a lung cancer model.