ROS-Responsive Nanoparticle Delivery of mRNA and Photosensitizer for Combinatorial Cancer Therapy.
Hui ZhouYuqin LiaoXiangfei HanDean Shuailin ChenXuechuan HongKun ZhouXingya JiangYuling XiaoJin-Jun ShiPublished in: Nano letters (2023)
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.
Keyphrases
- photodynamic therapy
- cancer therapy
- reactive oxygen species
- fluorescence imaging
- binding protein
- cell death
- induced apoptosis
- dna damage
- drug delivery
- papillary thyroid
- poor prognosis
- signaling pathway
- endoplasmic reticulum stress
- lymph node metastasis
- climate change
- risk assessment
- stem cells
- multidrug resistant
- long non coding rna
- high throughput
- human health
- childhood cancer
- iron oxide