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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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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. |
format | Online Article Text |
id | pubmed-7886705 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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