An antifouling membrane-fusogenic liposome for effective intracellular delivery in vivo

Huimin Kong, Chunxiong Zheng, Ke Yi, Rachel L. Mintz, Yeh-Hsing Lao, Yu Tao and Mingqiang Li ()
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Huimin Kong: Sun Yat-sen University
Chunxiong Zheng: Sun Yat-sen University
Ke Yi: Sun Yat-sen University
Rachel L. Mintz: Washington University in St. Louis
Yeh-Hsing Lao: The State University of New York
Yu Tao: Sun Yat-sen University
Mingqiang Li: Sun Yat-sen University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract The membrane-fusion-based internalization without lysosomal entrapment is advantageous for intracellular delivery over endocytosis. However, protein corona formed on the membrane-fusogenic liposome surface converts its membrane-fusion performance to lysosome-dependent endocytosis, causing poorer delivery efficiency in biological conditions. Herein, we develop an antifouling membrane-fusogenic liposome for effective intracellular delivery in vivo. Leveraging specific lipid composition at an optimized ratio, such antifouling membrane-fusogenic liposome facilitates fusion capacity even in protein-rich conditions, attributed to the copious zwitterionic phosphorylcholine groups for protein-adsorption resistance. Consequently, the antifouling membrane-fusogenic liposome demonstrates robust membrane-fusion-mediated delivery in the medium with up to 38% fetal bovine serum, outclassing two traditional membrane-fusogenic liposomes effective at 4% and 6% concentrations. When injected into mice, antifouling membrane-fusogenic liposomes can keep their membrane-fusion-transportation behaviors, thereby achieving efficient luciferase transfection and enhancing gene-editing-mediated viral inhibition. This study provides a promising tool for effective intracellular delivery under complex physiological environments, enlightening future nanomedicine design.

Date: 2024
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DOI: 10.1038/s41467-024-46533-z

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