Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles

Lixue Wang, Guosheng Wang, Wenjun Mao, Yundi Chen, Md. Mofizur Rahman, Chuandong Zhu, Peter M. Prisinzano, Bo Kong, Jing Wang (), Luke P. Lee () and Yuan Wan ()
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Lixue Wang: Nanjing University of Chinese Medicine
Guosheng Wang: Binghamton University
Wenjun Mao: Binghamton University
Yundi Chen: Binghamton University
Md. Mofizur Rahman: Binghamton University
Chuandong Zhu: Nanjing University of Chinese Medicine
Peter M. Prisinzano: Binghamton University
Bo Kong: Heidelberg University Hospital
Jing Wang: Yizheng Hospital of Nanjing Drum Tower Hospital Group
Luke P. Lee: Brigham and Women’s Hospital, Harvard Medical School
Yuan Wan: Binghamton University

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-39181-2

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