Optimization of the Linker Length of Mannose-Cholesterol Conjugates for Enhanced mRNA Delivery to Dendritic Cells by Liposomes

Frontiers in Pharmacology
Fazhan WangXiangrong Song

Abstract

Liposomes (LPs) as commonly used mRNA delivery systems remain to be rationally designed and optimized to ameliorate the antigen expression of mRNA vaccine in dendritic cells (DCs). In this study, we synthesized mannose-cholesterol conjugates (MPn-CHs) by click reaction using different PEG units (PEG100, PEG1000, and PEG2000) as linker molecules. MPn-CHs were fully characterized and subsequently used to prepare DC-targeting liposomes (MPn-LPs) by a thin-film dispersion method. MPn-LPs loaded with mRNA (MPn-LPX) were finally prepared by a simple self-assembly method. MPn-LPX displayed bigger diameter (about 135 nm) and lower zeta potential (about 40 mV) compared to MPn-LPs. The in vitro transfection experiment on DC2.4 cells demonstrated that the PEG length of mannose derivatives had significant effect on the expression of GFP-encoding mRNA. MP1000-LPX containing MP1000-CH can achieve the highest transfection efficiency (52.09 ± 4.85%), which was significantly superior to the commercial transfection reagent Lipo 3K (11.47 ± 2.31%). The optimal DC-targeting MP1000-LPX showed an average size of 132.93 ± 4.93 nm and zeta potential of 37.93 ± 2.95 mV with nearly spherical shape. Moreover, MP1000-LPX can protect mRNA against degradati...Continue Reading

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Citations

Feb 6, 2020·Pharmaceutics·Abishek WadhwaAneesh Thakur
Nov 11, 2020·The Journal of Gene Medicine·Jiaxi HeA James Mixson
Feb 18, 2021·Molecular Cancer·Yang WangXiawei Wei
Feb 24, 2020·Biotechnology Advances·Yuhua WengYuanyu Huang
Feb 27, 2021·Molecular Cancer·Lei MiaoLeaf Huang
May 25, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hai HuangXiangrong Song

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Methods Mentioned

BETA
transfection
column chromatography
infrared spectroscopy
flow cytometry
transmission electron microscopy
electron microscopy
Electrophoresis
Assay.
for

Software Mentioned

FlowJo

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