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

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ROS-Responsive Nanoparticle Delivery of mRNA and Photosensitizer for Combinatorial Cancer Therapy
Nano Letters ( IF 9.6 ) Pub Date : 2023-04-24 , DOI: 10.1021/acs.nanolett.2c03784
Hui Zhou _{1,

2,

3} , Yuqin Liao ₁ , Xiangfei Han ₂ , Dean Shuailin Chen ₂ , Xuechuan Hong _{1,

4} , Kun Zhou ₅ , Xingya Jiang ₂ , Yuling Xiao ₂ , Jinjun Shi ₂

Affiliation

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.

中文翻译：

用于组合癌症治疗的 mRNA 和光敏剂的 ROS 响应纳米颗粒递送

信使 RNA (mRNA) 疗法已显示出治疗包括癌症在内的不同疾病的巨大潜力。虽然 mRNA 已作为抗原广泛用于癌症疫苗开发或作为免疫调节剂用于癌症免疫治疗，但尚未在癌症治疗中探索 mRNA 疗法与光动力疗法的结合。在此，我们报告了一种活性氧 (ROS) 响应性聚合物纳米颗粒 (NP) 平台，用于 mRNA 和光敏剂的首次现场共递送，用于有效的癌症治疗。我们开发了基于 ROS 响应性低聚物的聚合物 NP，并将它们应用于测试 p53 mRNA 和吲哚菁绿 (ICG) 的组合。ROS 触发的 NPs 分解可以提高 mRNA 翻译效率，从而 p53 表达诱导肺肿瘤细胞凋亡。同时，释放的 ICG 在 808 nm 激光照射下可导致 ROS 的产生，从而诱导光动力疗法。p53 mRNA 和 ICG 的 NP 协同递送在肺癌模型中显示出有效且安全的抗肿瘤作用。

更新日期：2023-04-24

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