Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

Detail(s)

Original languageEnglish
Article numbere12057
Journal / PublicationJournal of Extracellular Vesicles
Volume10
Issue number4
Online published16 Feb 2021
Publication statusPublished - Feb 2021

Link(s)

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.

Research Area(s)

  • conjugation, delivery, extracellular vesicles, targeted, therapeutics

Citation Format(s)

Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery. / Pham, Tin Chanh; Jayasinghe, Migara Kavishka; Pham, Thach Tuan; Yang, Yuqi; Wei, Likun; Waqas, Muhammad Usman; 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.

In: Journal of Extracellular Vesicles, Vol. 10, No. 4, e12057, 02.2021.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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