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

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 betwee...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886705/
https://www.ncbi.nlm.nih.gov/pubmed/33643546
http://dx.doi.org/10.1002/jev2.12057
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author 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.
author_facet 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.
author_sort Pham, Tin Chanh
collection PubMed
description 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.
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spelling pubmed-78867052021-02-26 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 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. J Extracell Vesicles Research Articles 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. John Wiley and Sons Inc. 2021-02-16 2021-02 /pmc/articles/PMC7886705/ /pubmed/33643546 http://dx.doi.org/10.1002/jev2.12057 Text en © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
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.
Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery
title Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery
title_full Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery
title_fullStr Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery
title_full_unstemmed Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery
title_short Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery
title_sort covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886705/
https://www.ncbi.nlm.nih.gov/pubmed/33643546
http://dx.doi.org/10.1002/jev2.12057
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