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Title: Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery
Authors: Pham, Tin Chanh
Jayasinghe, Migara Kavishka
Pham, Thach Tuan 
Yang, Yuqi
Wei, Likun
Usman, Waqas Muhammad
Chen, Huan
Pirisinu, Marco
Gong, Jinhua
Kim, Seongkyeol
Peng, Boya 
Wang, Weixi
Chan, Charlene 
Ma, Victor
Nguyen, Nhung T. H.
Kappei, Dennis 
Nguyen, Xuan-Hung
Cho, William C.
Shi, Jiahai
Le, Minh T. N. 
Keywords: conjugation
extracellular vesicles
Issue Date: 1-Feb-2021
Publisher: John Wiley and Sons Inc
Citation: Pham, Tin Chanh, Jayasinghe, Migara Kavishka, Pham, Thach Tuan, Yang, Yuqi, Wei, Likun, Usman, Waqas Muhammad, Chen, Huan, Pirisinu, Marco, Gong, Jinhua, Kim, Seongkyeol, Peng, Boya, Wang, Weixi, Chan, Charlene, Ma, Victor, Nguyen, Nhung T. H., Kappei, Dennis, Nguyen, Xuan-Hung, Cho, William C., Shi, Jiahai, Le, Minh T. N. (2021-02-01). Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery. Journal of Extracellular Vesicles 10 (4) : e12057. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Natural extracellular vesicles (EVs) are ideal drug carriers due to their remarkable biocompatibility. Their delivery specificity can be achieved by the conjugation of targeting ligands. However, existing methods to engineer target-specific EVs are tedious or inefficient, having to compromise between harsh chemical treatments and transient interactions. Here, we describe a novel method for the covalent conjugation of EVs with high copy numbers of targeting moieties using protein ligases. Conjugation of EVs with either an epidermal growth factor receptor (EGFR)-targeting peptide or anti-EGFR nanobody facilitates their accumulation in EGFR-positive cancer cells, both in vitro and in vivo. Systemic delivery of paclitaxel by EGFR-targeting EVs at a low dose significantly increases drug efficacy in a xenografted mouse model of EGFR-positive lung cancer. The method is also applicable to the conjugation of EVs with peptides and nanobodies targeting other receptors, such as HER2 and SIRP alpha, and the conjugated EVs can deliver RNA in addition to small molecules, supporting the versatile application of EVs in cancer therapies. This simple, yet efficient and versatile method for the stable surface modification of EVs bypasses the need for genetic and chemical modifications, thus facilitating safe and specific delivery of therapeutic payloads to target cells. © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles
Source Title: Journal of Extracellular Vesicles
ISSN: 2001-3078
DOI: 10.1002/jev2.12057
Rights: Attribution 4.0 International
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