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Assessing the conjugation efficiency of surface-modified extracellular vesicles using single nanovesicle analysis
Leora Goldbloom-Helzner1,2,3, Harjn Bains3, Emma G Loll1,2
1Center for Surgical Bioengineering, Department of Surgery, School of Medicine, University of California-Davis, Sacramento, CA, 95817, USA. aawang@ucdavis.edu.
Nanoscale
|September 23, 2024
Summary
Researchers engineered extracellular vesicles (EVs) at the single-vesicle level for targeted drug delivery. This novel approach overcomes EV heterogeneity, enabling precise surface modification for enhanced therapeutic applications.
Area of Science:
- Biotechnology
- Nanomedicine
- Cell Biology
Background:
- Extracellular vesicles (EVs) are crucial for intercellular communication and hold therapeutic potential.
- Current limitations in targeted *in vivo* delivery hinder clinical translation of EVs.
- EV surface modification is key for specific cell uptake and biodistribution control.
Purpose of the Study:
- To engineer the surface of extracellular vesicles (EVs) at the single-vesicle level.
- To develop and validate orthogonal platforms for precise aptamer conjugation to single EVs.
- To assess the impact of EV size on aptamer conjugation efficiency and EV integrity.
Main Methods:
- Engineered single extracellular vesicles (EVs) using lipid insertion and covalent protein modification.
- Utilized orthogonal platforms with single vesicle resolution to conjugate myelin-targeting aptamers (LJM-3064).
- Assessed single-EV integrity, stability, and aptamer conjugation efficiency using advanced single-vesicle analysis.
Main Results:
- Achieved aptamer conjugation to single EVs with size-dependent efficiency.
- Demonstrated the feasibility of engineering EV surfaces at the single-vesicle level.
- Validated the integrity and stability of modified single EVs (Apt-EVs).
Conclusions:
- Single-vesicle analysis is critical for overcoming EV heterogeneity in therapeutic engineering.
- Developed a novel single-EV-based framework for precise surface modification.
- This approach enhances the potential of EVs for targeted drug delivery and cell-specific therapies.
