Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies.

ABSTRACT: Background: As the overwhelming majority of advanced mRNA delivery systems are preferentially accumulated in the liver, there is an accelerating growth in the demand for the development of non-liver mRNA delivery platforms. Methods: In this study, we prepared cationic lipid-like nanoassemblies through a N-quaternizing strategy. Their physicochemical properties, in vitro mRNA delivery efficiency, and organ tropism in mice were investigated. Results: Introduction of quaternary ammonium groups onto lipid-like nanoassemblies not only enhances their mRNA delivery performance in vitro, but also completely alters their tropism from the spleen to the lung after intravenous administration in mice. Quaternized lipid-like nanoassemblies exhibit ultra-high specificity to the lung

SUBMITTER: Huang Y 

PROVIDER: S-EPMC10758058 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature