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

Author

Listed:
  • Huimin Kong

    (Sun Yat-sen University)

  • Chunxiong Zheng

    (Sun Yat-sen University
    South China Normal 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)

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.

Suggested Citation

  • Huimin Kong & Chunxiong Zheng & Ke Yi & Rachel L. Mintz & Yeh-Hsing Lao & Yu Tao & Mingqiang Li, 2024. "An antifouling membrane-fusogenic liposome for effective intracellular delivery in vivo," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46533-z
    DOI: 10.1038/s41467-024-46533-z
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    References listed on IDEAS

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    1. Martin P. Stewart & Armon Sharei & Xiaoyun Ding & Gaurav Sahay & Robert Langer & Klavs F. Jensen, 2016. "In vitro and ex vivo strategies for intracellular delivery," Nature, Nature, vol. 538(7624), pages 183-192, October.
    2. Francesca Giulimondi & Luca Digiacomo & Daniela Pozzi & Sara Palchetti & Elisabetta Vulpis & Anna Laura Capriotti & Riccardo Zenezini Chiozzi & Aldo Laganà & Heinz Amenitsch & Laura Masuelli & Giovann, 2019. "Interplay of protein corona and immune cells controls blood residency of liposomes," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
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