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Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles

Author

Listed:
  • Lixue Wang

    (Nanjing University of Chinese Medicine
    Binghamton University)

  • Guosheng Wang

    (Binghamton University
    Tongji University School of Medicine)

  • Wenjun Mao

    (Binghamton University
    The Affiliated Wuxi People’s Hospital of Nanjing Medical University)

  • Yundi Chen

    (Binghamton University)

  • Md. Mofizur Rahman

    (Binghamton University)

  • Chuandong Zhu

    (Nanjing University of Chinese Medicine
    Binghamton University)

  • Peter M. Prisinzano

    (Binghamton University)

  • Bo Kong

    (Heidelberg University Hospital)

  • Jing Wang

    (Yizheng Hospital of Nanjing Drum Tower Hospital Group
    The Affiliated Drum Tower Hospital of Nanjing University Medical School)

  • Luke P. Lee

    (Brigham and Women’s Hospital, Harvard Medical School
    University of California, Berkeley
    University of California at Berkeley
    Sungkyunkwan University)

  • Yuan Wan

    (Binghamton University)

Abstract

Cell-derived small extracellular vesicles have been exploited as potent drug vehicles. However, significant challenges hamper their clinical translation, including inefficient cytosolic delivery, poor target-specificity, low yield, and inconsistency in production. Here, we report a bioinspired material, engineered fusogen and targeting moiety co-functionalized cell-derived nanovesicle (CNV) called eFT-CNV, as a drug vehicle. We show that universal eFT-CNVs can be produced by extrusion of genetically modified donor cells with high yield and consistency. We demonstrate that bioinspired eFT-CNVs can efficiently and selectively bind to targets and trigger membrane fusion, fulfilling endo-lysosomal escape and cytosolic drug delivery. We find that, compared to counterparts, eFT-CNVs significantly improve the treatment efficacy of drugs acting on cytosolic targets. We believe that our bioinspired eFT-CNVs will be promising and powerful tools for nanomedicine and precision medicine.

Suggested Citation

  • Lixue Wang & Guosheng Wang & Wenjun Mao & Yundi Chen & Md. Mofizur Rahman & Chuandong Zhu & Peter M. Prisinzano & Bo Kong & Jing Wang & Luke P. Lee & Yuan Wan, 2023. "Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39181-2
    DOI: 10.1038/s41467-023-39181-2
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    References listed on IDEAS

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    1. Wei Gao & Zhewei Tang & Yi-Fan Zhang & Mingqian Feng & Min Qian & Dimiter S. Dimitrov & Mitchell Ho, 2015. "Immunotoxin targeting glypican-3 regresses liver cancer via dual inhibition of Wnt signalling and protein synthesis," Nature Communications, Nature, vol. 6(1), pages 1-12, May.
    2. Sushrut Kamerkar & Valerie S. LeBleu & Hikaru Sugimoto & Sujuan Yang & Carolina F. Ruivo & Sonia A. Melo & J. Jack Lee & Raghu Kalluri, 2017. "Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer," Nature, Nature, vol. 546(7659), pages 498-503, June.
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