Rational design of lipid nanoparticles: overcoming physiological barriers for selective intracellular mRNA delivery

IF 5.3 2区材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY ACS Applied Nano Materials Pub Date : 2024-07-13 DOI:10.1016/j.cbpa.2024.102499

Yu Zhao , Zeyu Morgan Wang , Donghui Song , Mengting Chen, Qiaobing Xu

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Abstract

This review introduces the typical delivery process of messenger RNA (mRNA) nanomedicines and concludes that the delivery involves a at least four-step SCER cascade and that high efficiency at every step is critical to guarantee high overall therapeutic outcomes. This SCER cascade process includes selective organ-targeting delivery, cellular uptake, endosomal escape, and cytosolic mRNA release. Lipid nanoparticles (LNPs) have emerged as a state-of-the-art vehicle for in vivo mRNA delivery. The review emphasizes the importance of LNPs in achieving selective, efficient, and safe mRNA delivery. The discussion then extends to the technical and clinical considerations of LNPs, detailing the roles of individual components in the SCER cascade process, especially ionizable lipids and helper phospholipids. The review aims to provide an updated overview of LNP-based mRNA delivery, outlining recent innovations and addressing challenges while exploring future developments for clinical translation over the next decade.

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合理设计脂质纳米颗粒：克服生理障碍，选择性地在细胞内输送 mRNA。

这篇综述介绍了信使核糖核酸（mRNA）纳米药物的典型递送过程，并得出结论认为，递送过程涉及至少四个步骤的 SCER 级联，而每个步骤的高效率是保证高总体治疗效果的关键。这一 SCER 级联过程包括选择性器官靶向递送、细胞摄取、内体逸出和细胞膜 mRNA 释放。脂质纳米颗粒（LNPs）已成为体内递送 mRNA 的最先进载体。综述强调了 LNPs 在实现选择性、高效和安全递送 mRNA 方面的重要性。然后讨论了 LNPs 的技术和临床考虑因素，详细介绍了 SCER 级联过程中各个成分的作用，尤其是可电离脂质和辅助磷脂。本综述旨在提供基于 LNP 的 mRNA 递送的最新概况，概述最近的创新并应对挑战，同时探讨未来十年临床转化的发展。

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来源期刊

ACS Applied Nano Materials Multiple-

CiteScore

8.30

自引率

3.40%

发文量

1601

期刊介绍： ACS Applied Nano Materials is an interdisciplinary journal publishing original research covering all aspects of engineering, chemistry, physics and biology relevant to applications of nanomaterials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important applications of nanomaterials.