Open AccessCovalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery
Author(s) -
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 XuanHung,
Cho William C.,
Shi Jiahai,
Le Minh T.N.
Publication year - 2021
Publication title -
journal of extracellular vesicles
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.94
H-Index - 68
ISSN - 2001-3078
DOI - 10.1002/jev2.12057
Subject(s) - paclitaxel , in vivo , drug delivery , extracellular vesicles , epidermal growth factor receptor , chemistry , peptide , targeted drug delivery , cancer research , microbiology and biotechnology , receptor , nanotechnology , cancer , biochemistry , biology , materials science , genetics
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.