Ionizable Lipids with Branched Linkers Enhance the Delivery of mRNA Vaccines

IF 8.3 2区材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY

ACS Applied Materials & Interfaces Pub Date : 2025-02-20 DOI:10.1021/acsami.4c21289

Jiwei Liu, Wenjing Sun, Bing Xiao, Haoran Xu, Jiaqi Fan, Xueying Shi, Yixuan Pan, Qi Wei, Ruoshui Li, Huimin Wang, Ying Piao, Jiajia Xiang, Shiqun Shao, Zhuxian Zhou, Youqing Shen, Jianbin Tang

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引用次数: 0

Abstract

The emergence of mRNA vaccines has heralded an epoch in disease prevention and treatment. Safe and efficient mRNA delivery systems are highly desired for the widespread application of mRNA therapeutics. Herein, we have designed a facile synthetic pathway for producing ionizable lipids featuring various branched linkers. These lipids have been integrated into lipid nanoparticles (LNPs) to improve the delivery of mRNA vaccines. The influence of linker structure on lipids and LNPs is currently underreported, yet it undeniably exerts a substantial impact on the outcomes. Through systematic screening and formulation optimization, we have identified that LNPs comprising ionizable lipids with a branched β-isobutylglutarate linker (bLNPs) exhibited superior transfection capabilities. In preclinical cancer prevention and treatment models, mRNA vaccines delivered by bLNPs (mRNA-bLNPs) have shown significant efficacy without causing systemic toxicity, highlighting the potential of bLNPs for clinical translation. Our synthetic strategy facilitates the expansion of the LNP library and provides valuable insights into the relationship between linker structures and delivery efficiency, thereby propelling the advancement of LNP technology.

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来源期刊

ACS Applied Materials & Interfaces 工程技术-材料科学：综合

CiteScore

16.00

自引率

6.30%

发文量

4978

审稿时长

1.8 months

期刊介绍： ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.