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Updated: Dec 22, 2025

Characterizing Extracellular Vesicles from Biological Fluids
Published on: February 28, 2025
Surface functionalization strategies of extracellular vesicles.
Sagar Rayamajhi1, Santosh Aryal
1Department of Chemistry, Nanotechnology Innovation Center of Kansas State (NICKS), Kansas State University, Manhattan, KS 66506, USA. saryal@ksu.edu.
This review categorizes extracellular vesicle (EV) surface functionalization into physical, biological, and chemical methods. These strategies enhance EV applications in diagnostics and therapeutics by adding specific functionalities.
Area of Science:
- Biotechnology
- Cell Biology
- Nanomedicine
Background:
- Extracellular vesicles (EVs) are cell-secreted vesicles involved in intercellular communication.
- EVs possess rich molecular cargo, making them promising for biomedical applications like drug delivery and diagnostics.
- Functionalizing EVs enhances their specificity and utility in various biomedical fields.
Purpose of the Study:
- To review and classify existing surface functionalization strategies for extracellular vesicles (EVs).
- To compare the advantages and limitations of different EV functionalization approaches.
- To highlight the potential of optimized functionalization for advancing EV-based therapies and diagnostics.
Main Methods:
- Categorization of EV surface functionalization into physical, biological, and chemical approaches.
- Discussion of specific techniques within each category, including sonication, genetic engineering, and click chemistry (e.g., thiol-maleimide, azide-alkyne).
- Comparative analysis of the presented functionalization strategies.
Main Results:
- Identified three primary strategies for EV surface functionalization: physical, biological, and chemical.
- Detailed various methods within each strategy, such as membrane rearrangement, cell engineering, and covalent conjugation.
- Emphasized the potential for combining approaches to overcome limitations and improve EV functionality.
Conclusions:
- Surface functionalization is crucial for expanding the biomedical applications of EVs.
- Physical, biological, and chemical methods offer distinct advantages for modifying EV surfaces.
- Optimized and potentially combined functionalization strategies can enhance EV integrity and efficacy for therapeutic and diagnostic purposes.
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