Surface Functionalization of Exosomes Using Click Chemistry
Open accessAbstract
A method for conjugation of ligands to the surface of exosomes was developed using click chemistry. Copper-catalyzed azide alkyne cycloaddition (click chemistry) is ideal for biocojugation of small molecules and macromolecules to the surface of exosomes, due to fast reaction times, high specificity, and compatibility in aqueous buffers. Exosomes cross-linked with alkyne groups using carbodiimide chemistry were conjugated to a model azide, azide-fluor 545. Conjugation had no effect on the size of exosomes, nor was there any change in the extent of exosome adherence/internalization with recipient cells, suggesting the reaction conditions were mild on exosome structure and function. We further investigated the extent of exosomal protein modification with alkyne groups. Using liposomes with surface alkyne groups of a similar size and concentration to exosomes, we estimated that approximately 1.5 alkyne groups were present for every 150 kDa of exosomal protein.
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Current methods of loading therapeutic molecules into EVs are limited by low efficiency, toxicity and lack of scalability.
“Current methods of loading therapeutic molecules into EVs such as electroporation, genetic engineering of host cells and chemical conjugation, are limited by low efficiency, toxicity and lack of scalability20,21.”
From GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain (2021) · cites this paper as [21]
The Introduction (page unavailable) says a surface targeting moiety may be needed for efficient exosome delivery, but does not assess the efficiency of loading therapeutic molecules. The Discussion (page unavailable) describes click-chemistry surface functionalization; our copy does not address whether electroporation, host-cell engineering, or chemical conjugation are limited by loading efficiency, toxicity, or scalability. Searches for those methods and limitations found no supporting passage. (LLM, conf=0.72)
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- Authors
- Smyth, T., Petrova, K., Payton, N. M., Persaud, I., Redzic, J. S., Graner, M. W., Smith-Jones, P., & Anchordoquy, T. J.
- Affiliations
- University of Colorado Anschutz (US)
- Stony Brook School (US)
- Corresponding author
- Anchordoquy, Thomas J.
- Venue
- Bioconjugate Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-09-15
- Volume
- 25
- Issue
- 10
- Pages
- 1777-1784
- ISSN
- 1043-1802 (ISSN-L)
- 1520-4812
- PMC
- PMC4198107
- OpenAlex
- W2330369687
- Cited by
- 532
- References
- 0
- Citations by year
- 2026: 72 · 2025: 74 · 2024: 70 · 2023: 89 · 2022: 49 · 2021: 52 · 2020: 42 · 2019: 34 · 2018: 19 · 2017: 12 · 2016: 11 · 2015: 7 · 2014: 1
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Bioconjugate Chemistry (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Biomedical Imaging and Bioengineering (1RO1 EB016378)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- exosomes, surface functionalization, click chemistry, copper-catalyzed azide-alkyne cycloaddition, ligand conjugation, carbodiimide chemistry, exosome internalization, liposomes
- MeSH terms
- Alkynes, Animals, Azides, Cell Line, Copper, Cross-Linking Reagents, Surface Properties, Mice, Exosomes, Click Chemistry, Cycloaddition Reaction
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