Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery
Open accessAbstract
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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REG1 has been used to encapsulate mRNA into exosomes post-separation.
“Moreover, a loading reagent called REG1 has been used to encapsulate mRNA into exosomes post-separation [114].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [114]
RBCEV modified by binding to nanobodies targeting α-EGFR and α-HER2 demonstrated specific uptake by lung tumor cells expressing EGFR in vivo.
“In addition, the system demonstrated specific uptake of RBCEV by lung tumor cells expressing EGFR in vivo [114].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [114]
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- Authors
- Pham, T. C., Jayasinghe, M. K., Pham, T. T., Yang, Y., Wei, L., Usman, W. M., Chen, H., Pirisinu, M., Gong, J., Kim, S., Peng, B., Wang, W., Chan, C., Ma, V., Nguyen, N. T. H., Kappei, D., Nguyen, X., Cho, W. C., Shi, J., & Le, M. T. N.
- Affiliations
- National University of Singapore (SG)
- City University of Hong Kong (HK)
- Queen Elizabeth Hospital (CN)
- VinUniversity (VN)
- Corresponding author
- Shi, Jiahai
- Le, Minh T.N.
- ORCID
- Venue
- Journal of Extracellular Vesicles
- Publisher
- Wiley
- Published
- 2021-02
- Volume
- 10
- Issue
- 4
- Pages
- e12057-e12057
- ISSN
- 2001-3078 (ISSN-L)
- PMC
- PMC7886705
- OpenAlex
- W3131515933
- Cited by
- 250
- References
- 38
- Citations by year
- 2026: 51 · 2025: 53 · 2024: 42 · 2023: 51 · 2022: 41 · 2021: 12
- FWCI
- 11.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Extracellular Vesicles (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- CityU Scholars (submittedVersion, cc-by)
- Funders
- National Research Foundation
- National University of Singapore (NUHSRO/2019/076/STARTUP/02)
- National Research Foundation Singapore
- National Natural Science Foundation of China (81773246, 81770099, 81972865)
- Innovation and Technology Commission
- Innovation and Technology Fund
- Health and Medical Research Fund (05160296, 06172196)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- extracellular vesicles, covalent conjugation, targeting ligands, nanobodies, EGFR-positive lung cancer, paclitaxel delivery, targeted drug delivery, HER2, SIRPα, RNA delivery, surface modification, cancer therapy
- MeSH terms
- Extracellular Vesicles, Animals, Antineoplastic Agents, Phytogenic, Drug Carriers, Erythrocytes, Humans, Lung Neoplasms, Peptides, Drug Delivery Systems, Paclitaxel, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice, Single-Domain Antibodies, ErbB Receptors
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