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mRNA 靶向递送至免疫细胞以增强癌症治疗的进展。

Advances in targeted delivery of mRNA into immune cells for enhanced cancer therapy.

机构信息

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P. R. China.

Guangzhou Key Laboratory of Medical Nanomaterials, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P. R. China.

出版信息

Theranostics. 2024 Sep 3;14(14):5528-5550. doi: 10.7150/thno.93745. eCollection 2024.

DOI:10.7150/thno.93745
PMID:39310113
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11413781/
Abstract

Messenger RNA (mRNA) therapy has been applied to the treatment of various human diseases including malignant tumors. Increasing evidences have shown that mRNA can enhance the efficacy of cancer immunotherapy by modulating the functions of immune cells and stimulating their activity. However, mRNA is a type of negatively charged biomacromolecules that are susceptible to serum nucleases and cannot readily cross the cell membrane. In the past few decades, various nanoparticles (NPs)-based delivery systems have been rationally designed and developed to facilitate the intracellular uptake and cytosolic delivery of mRNA. More importantly, by means of the specific recognition between the targeting ligands decorated on NP surface and receptors specifically expressed on immune cells, these mRNA delivery systems could be functionalized to target immune cells to further enhance the mRNA-based cancer immunotherapy. In this review, we briefly introduced the advancements of mRNA in cancer therapy, discussed the challenges faced by mRNA delivery, and systematically summarized the recent development in NPs-based mRNA delivery systems targeting various types of immune cells for cancer immunotherapy. The future development of NPs-mediated targeted mRNA delivery and their challenges in clinical translation are also discussed.

摘要

信使 RNA（mRNA）疗法已被应用于治疗包括恶性肿瘤在内的各种人类疾病。越来越多的证据表明，mRNA 通过调节免疫细胞的功能并刺激其活性，能够增强癌症免疫疗法的疗效。然而，mRNA 是一种带负电荷的生物大分子，容易受到血清核酸酶的影响，并且不易穿过细胞膜。在过去的几十年中，已经合理设计和开发了各种基于纳米粒子（NP）的递药系统，以促进 mRNA 的细胞内摄取和细胞质内递送。更重要的是，通过 NP 表面上修饰的靶向配体与免疫细胞上特异性表达的受体之间的特异性识别，这些 mRNA 递药系统可以被功能化以靶向免疫细胞，从而进一步增强基于 mRNA 的癌症免疫疗法。在这篇综述中，我们简要介绍了 mRNA 在癌症治疗方面的进展，讨论了 mRNA 递药所面临的挑战，并系统总结了基于 NP 的针对各种类型免疫细胞的 mRNA 递药系统在癌症免疫治疗中的最新发展。还讨论了 NPs 介导的靶向 mRNA 递药的未来发展及其在临床转化中的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243a/11413781/b180736f5add/thnov14p5528g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243a/11413781/878c42bfa008/thnov14p5528g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243a/11413781/b180736f5add/thnov14p5528g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243a/11413781/878c42bfa008/thnov14p5528g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243a/11413781/8260ef54d8d4/thnov14p5528g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243a/11413781/11996bc7eac3/thnov14p5528g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243a/11413781/39dac3918bac/thnov14p5528g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243a/11413781/fa27e0d68ce6/thnov14p5528g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243a/11413781/ac010f6240ce/thnov14p5528g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243a/11413781/a1a5a61baee8/thnov14p5528g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243a/11413781/6f7449db16c9/thnov14p5528g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243a/11413781/b180736f5add/thnov14p5528g009.jpg

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