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

Huang，Yixuan1; Wu，Jiacai1,2; Li，Sanpeng1; Liu，Zhen1; Li，Zhenghua1; Zhou，Boping1,2; Li，Bin1,2

2024

10.7150/thno.90071

Theranostics   影响因子和分区

1838-7640

1838-7640

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 and are predominantly taken up by pulmonary immune cells, leading to over 95% of exogenous mRNA translation in the lungs. Such mRNA delivery carriers are stable even after more than one-year storage at ambient temperature. Conclusions: Quaternization provides an alternative method for design of new lung-targeted mRNA delivery systems without incorporation of targeting ligands, which should extend the therapeutic applicability of mRNA to lung diseases.

lipid-like nanoassembly lung targeting quaternization systemic mRNA delivery ultra-high selectivity

SCI

英语

第一

Shenzhen Science and Technology Program[RCYX20200714114539061] ; National Natural Science Foundation of China[82072053]

Research & Experimental Medicine

Medicine, Research & Experimental

WOS:001141907600020

IVYSPRING INT PUBL

2-s2.0-85181568897

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.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China

Huang，Yixuan,Wu，Jiacai,Li，Sanpeng,et al. Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies[J]. Theranostics,2024,14(2):830-842.

Huang，Yixuan.,Wu，Jiacai.,Li，Sanpeng.,Liu，Zhen.,Li，Zhenghua.,...&Li，Bin.(2024).Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies.Theranostics,14(2),830-842.

Huang，Yixuan,et al."Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies".Theranostics 14.2(2024):830-842.