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信使核糖核酸纳米递送系统：靶向策略与给药途径

mRNA nanodelivery systems: targeting strategies and administration routes.

作者信息

Yuan Mujie, Han Zeyu, Liang Yan, Sun Yong, He Bin, Chen Wantao, Li Fan

机构信息

Department of Oral Implantology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.

Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao, 266073, China.

出版信息

Biomater Res. 2023 Sep 22;27(1):90. doi: 10.1186/s40824-023-00425-3.

DOI:10.1186/s40824-023-00425-3
PMID:37740246
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10517595/
Abstract

With the great success of coronavirus disease (COVID-19) messenger ribonucleic acid (mRNA) vaccines, mRNA therapeutics have gained significant momentum for the prevention and treatment of various refractory diseases. To function efficiently in vivo and overcome clinical limitations, mRNA demands safe and stable vectors and a reasonable administration route, bypassing multiple biological barriers and achieving organ-specific targeted delivery of mRNA. Nanoparticle (NP)-based delivery systems representing leading vector approaches ensure the successful intracellular delivery of mRNA to the target organ. In this review, chemical modifications of mRNA and various types of advanced mRNA NPs, including lipid NPs and polymers are summarized. The importance of passive targeting, especially endogenous targeting, and active targeting in mRNA nano-delivery is emphasized, and different cellular endocytic mechanisms are discussed. Most importantly, based on the above content and the physiological structure characteristics of various organs in vivo, the design strategies of mRNA NPs targeting different organs and cells are classified and discussed. Furthermore, the influence of administration routes on targeting design is highlighted. Finally, an outlook on the remaining challenges and future development toward mRNA targeted therapies and precision medicine is provided.

摘要

随着冠状病毒病（COVID-19）信使核糖核酸（mRNA）疫苗的巨大成功，mRNA疗法在预防和治疗各种难治性疾病方面获得了显著的发展势头。为了在体内有效发挥作用并克服临床局限性，mRNA需要安全稳定的载体和合理的给药途径，绕过多种生物屏障并实现mRNA的器官特异性靶向递送。基于纳米颗粒（NP）的递送系统是领先的载体方法，可确保将mRNA成功细胞内递送至靶器官。在这篇综述中，总结了mRNA的化学修饰以及各种类型的先进mRNA纳米颗粒，包括脂质纳米颗粒和聚合物。强调了被动靶向尤其是内源性靶向以及主动靶向在mRNA纳米递送中的重要性，并讨论了不同的细胞内吞机制。最重要的是，基于上述内容以及体内各种器官的生理结构特征，对靶向不同器官和细胞的mRNA纳米颗粒的设计策略进行了分类和讨论。此外，突出了给药途径对靶向设计的影响。最后，对mRNA靶向治疗和精准医学的剩余挑战和未来发展进行了展望。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10517595/aaff3d3e5f24/40824_2023_425_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10517595/132a1a314f97/40824_2023_425_Fig12_HTML.jpg
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