Affiliation:
1. School of Materials Science and Engineering Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education Guangdong Functional Biomaterials Engineering Technology Research Center Sun Yat-sen University Guangzhou 510006 China
2. College of Chemistry and Molecular Science Henan University Zhengzhou 450046 China
3. State Key Laboratory of Antiviral Drugs Henan University Zhengzhou 450046 China
Abstract
AbstractLipid nanoparticles (LNPs) are the most clinically successful drug delivery systems that have accelerated the development of mRNA drugs and vaccines. Among various structural components of LNPs, more recent attention has been paid in ionizable lipids (ILs) that was supposed as the key component in determining the effectiveness of LNPs for in vivo mRNA delivery. ILs are typically comprised of three moieties including ionizable heads, linkers, and hydrophobic tails, which suggested that the combination of different functional groups in three moieties could produce ILs with diverse chemical structures and biological identities. In this concept article, we provide a summary of chemical design strategy for high‐performing IL candidates and discuss their structure‐activity relationships for shifting tissue‐selective mRNA delivery. We also propose an outlook for the development of next‐generation ILs, enabling the broader translation of mRNA formulated with LNPs.
Funder
National Natural Science Foundation of China