Intracellular delivery of messenger RNA to macrophages with surfactant-derived lipid nanoparticles

Huang，Y.1; Yang，M.2; Wang，N.1,3; Li，S.1; Liu，Z.1; Li，Z.1; Ji，Z.2; Li，B.1,3

2022-12-01

10.1016/j.mtadv.2022.100295

Materials Today Advances   Impact Factor & Quartile

2590-0498

2590-0498

The broad biomedical applications of messenger RNA (mRNA)-based therapeutics rely heavily on the rapid development of mRNA delivery systems. In this study, dual-component lipid nanoparticles (LNPs) were developed for intracellular delivery of mRNA to macrophages. By screening a panel of quaternary ammonium compounds with varying alkyl or aryl side chains, a cationic surfactant containing two hexadecyl tails was found to be effective for mRNA delivery with the assistance of fusogenic lipids. Further investigating structure alterations and optimization of formulation parameters, we found that a surfactant-derived ionizable lipid mixed with a fusogenic lipid was capable of condensing mRNA and self-assembling into LNPs. Without using the PEGylated lipid, the resulting LNPs were able to render the exogenous mRNA resistant to hydrolysis by nucleases and displayed excellent biocompatibility, along with the capacity to deliver mRNA to hard-to-transfect. Overall, the dual-component nanocarrier provides a novel mRNA delivery platform for genetic engineering of macrophages.

Delivery system LNPs Macrophage mRNA PEGylation Quaternary ammonium compound Surfactant

SCI

English

First ; Corresponding

Natural Science Foundation of Shenzhen City[RCYX20200714114539061];

Materials Science

Materials Science, Multidisciplinary

WOS:000864020400005

ELSEVIER

2-s2.0-85138176981

Scopus

1.Department of Infectious Disease,Shenzhen People's Hospital,The First Affiliated Hospital of Southern University of Science and Technology & the Second Clinical Medical College of Jinan University,Shenzhen,518020,China
2.Department of Urology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100730,China
3.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China

Huang，Y.,Yang，M.,Wang，N.,et al. Intracellular delivery of messenger RNA to macrophages with surfactant-derived lipid nanoparticles[J]. Materials Today Advances,2022,16.

Huang，Y..,Yang，M..,Wang，N..,Li，S..,Liu，Z..,...&Li，B..(2022).Intracellular delivery of messenger RNA to macrophages with surfactant-derived lipid nanoparticles.Materials Today Advances,16.

Huang，Y.,et al."Intracellular delivery of messenger RNA to macrophages with surfactant-derived lipid nanoparticles".Materials Today Advances 16(2022).