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

IF 12.4 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Theranostics Pub Date : 2024-09-03 DOI:10.7150/thno.93745

Linzhuo Huang, Zhiquan Huang, Yuxuan Zhang, Chunhao Lin, Zixuan Zhao, Rong Li, Phei Er Saw, Xiaoding Xu

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引用次数: 0

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.

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将 mRNA 靶向传递到免疫细胞以增强癌症治疗的进展

信使核糖核酸（mRNA）疗法已被用于治疗包括恶性肿瘤在内的多种人类疾病。越来越多的证据表明，mRNA 可以通过调节免疫细胞的功能和刺激其活性来提高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，易受血清核酸酶的影响，不能轻易穿过细胞膜。在过去几十年中，人们合理地设计和开发了各种基于纳米颗粒（NPs）的递送系统，以促进 mRNA 在细胞内的吸收和在细胞膜上的递送。更重要的是，通过NP表面修饰的靶向配体与免疫细胞上特异表达的受体之间的特异性识别，这些mRNA递送系统可以功能化为靶向免疫细胞，从而进一步提高基于mRNA的癌症免疫疗法。在这篇综述中，我们简要介绍了 mRNA 在癌症治疗中的应用进展，讨论了 mRNA 递送所面临的挑战，并系统总结了基于 NPs 的 mRNA 递送系统靶向各类免疫细胞进行癌症免疫治疗的最新进展。此外，还讨论了 NPs 介导的靶向 mRNA 递送的未来发展及其在临床转化中面临的挑战。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

25.40

自引率

1.60%

发文量

433

审稿时长

1 months

期刊介绍： Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.