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

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapeutics

Background:

• Messenger RNA (mRNA) therapy shows promise for cancer treatment, primarily in vaccines and immunotherapy.
• The combination of mRNA therapy with photodynamic therapy (PDT) remains largely unexplored for cancer treatment.
• Developing novel drug delivery systems is crucial for enhancing therapeutic efficacy and safety.

Purpose of the Study:

• To develop a reactive oxygen species (ROS)-responsive polymeric nanoparticle (NP) platform for codelivering mRNA and photosensitizers.
• To investigate the synergistic anti-tumor effects of codelivering p53 mRNA and indocyanine green (ICG) using the developed NP system.
• To evaluate the efficacy and safety of this combined therapy in a lung cancer model.

Main Methods:

• Development of ROS-responsive oligomer-based polymeric nanoparticles for codelivery.
• Loading of p53 mRNA and indocyanine green (ICG) into the nanoparticles.
• In vitro and in vivo evaluation of NP performance, including ROS-triggered drug release, mRNA translation, apoptosis induction, and anti-tumor activity in a lung cancer model.

Main Results:

• The ROS-responsive NPs successfully codelivered p53 mRNA and ICG.
• ROS-triggered NP disassembly enhanced p53 mRNA translation, leading to apoptosis in lung tumor cells.
• The released ICG generated ROS under laser irradiation, inducing photodynamic therapy, resulting in a significant and safe anti-tumor effect.

Conclusions:

• The developed ROS-responsive nanoparticle platform enables effective codelivery of mRNA and photosensitizers.
• This combination therapy demonstrates significant potential for enhanced lung cancer treatment.
• The platform offers a promising strategy for synergistic cancer therapy by combining mRNA and photodynamic approaches.