Basic Guide for Approaching Drug Delivery with Extracellular Vesicles
Abstract
:1. Introduction
2. EV Biogenesis
3. Purification Methods
3.1. Size-Based Approaches
3.2. Precipitation-Based Methods
3.3. Affinity-Based Approaches
3.4. Chromatography Approaches
Method | Principle | Scalability | Yield (Recovery) | EV Damage | Purity | Equipment Requirement | Cost | Additional Pre/Post-Steps | Time | Ref. |
---|---|---|---|---|---|---|---|---|---|---|
Differential ultracentrifugation (dUC) | Serial UC steps | + | + (5–30%) | ↑↑↑ | ++ | +++ | + | No | ↑↑↑ | [22,24,25,26,27,28,29] |
Density gradient ultracentrifugation (DGU) | Separation of EVs by density using gradient medium | + | + (5–30%) | ↑ | ++++ | +++ | ++ | Yes (media removal) | ↑↑↑ | [12,22,31] |
Ultrafiltration (UF) | Filtration through semi-permeable membranes | +++ | +++ (30–80%) | ↑↑ | +++ | ++ | ++ | No | ↑/↑↑ | [12,22,32,33,34,35,36] |
Asymmetric depth filtration (DF) | Filtration through porous medium | ++ | ++ (40–60%) | ↑ | +++ | ++ | ++ | No | ↑↑ | [37] |
Tangential flow filtration (TFF) | Cross-flow filtration through membranes | ++++ | +++ (up to 90%) | ↑ | +++ | ++ | ++ | No | ↑↑ | [12,18,38,39,40,41] |
Precipitation approaches | EV sedimentation using polymers | +++ | ++++ (up to 90–95%) | ↑↑/↑↑↑ | + | + | ++ | Yes (polymer removal) | ↑↑↑ | [12,18,48,49,50] |
Affinity-based isolation | EV capture via specific interactions with EV markers | +/++ | ++ (50–70%) | ↑/↑↑ | ++++ | ++ | +++ | No | ↑↑ | [35,52,53,54,55,57] |
Size exclusion chromatography (SEC) | Separation by size through a bead-filled column | +++ (combined with UF/TFF) | ++ (40–75%) | ↑ | +++ | ++ | + | Yes (pre-Concentration) | ↑↑ | [43,44,45,46,47] |
Multimodal flowthrough chromatography (MFC) | Combination of size-exclusion and bind–elute chromatography | +++ (combined with pre-concentration) | ++/+++ (up to 80%) | ↑ | ++++ | ++ | ++ | Yes (pre-Concentration) | ↑↑ | [59] |
Anion-exchange chromatography (AIEX) | Binding of EVs to positively charged column | +++ | +++ (40–90%) | ↑↑ | ++ | ++ | ++ | Yes (buffer exchange) | ↑↑↑ | [43,61,62,63] |
3.5. Challenges of EV Preparation
4. EV Cargo Loading Methods
4.1. Endogenous Loading
4.1.1. Cells Transfection/Transduction for RNA Loading
4.1.2. EV-Associated Motifs for RNA Loading
4.1.3. Interaction of RNA with Proteins Enriched within EV Membranes
4.1.4. RNA Enrichment on the Plasma Membrane
4.2. Endogenous Protein Loading
- Fusing cargo to proteins enriched on EV membranes;
- Using post-translational modifications of the cargo proteins;
- Viral protein-assisted loading.
4.2.1. Fusion with Proteins Enriched within EV Membranes
4.2.2. Post-Translational Modifications of the Protein
4.2.3. Viral Protein-Assisted Loading
4.3. Exogenous Loading
4.3.1. Physical Methods
4.3.2. Chemical Methods
5. Challenges of Loading Cargo into EVs
6. Surface Display of Functional Moieties on EVs
7. Extracellular Vesicles in Clinical Practice
8. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Brezgin, S.; Danilik, O.; Yudaeva, A.; Kachanov, A.; Kostyusheva, A.; Karandashov, I.; Ponomareva, N.; Zamyatnin, A.A., Jr.; Parodi, A.; Chulanov, V.; et al. Basic Guide for Approaching Drug Delivery with Extracellular Vesicles. Int. J. Mol. Sci. 2024, 25, 10401. https://doi.org/10.3390/ijms251910401
Brezgin S, Danilik O, Yudaeva A, Kachanov A, Kostyusheva A, Karandashov I, Ponomareva N, Zamyatnin AA Jr., Parodi A, Chulanov V, et al. Basic Guide for Approaching Drug Delivery with Extracellular Vesicles. International Journal of Molecular Sciences. 2024; 25(19):10401. https://doi.org/10.3390/ijms251910401
Chicago/Turabian StyleBrezgin, Sergey, Oleg Danilik, Alexandra Yudaeva, Artyom Kachanov, Anastasiya Kostyusheva, Ivan Karandashov, Natalia Ponomareva, Andrey A. Zamyatnin, Jr., Alessandro Parodi, Vladimir Chulanov, and et al. 2024. "Basic Guide for Approaching Drug Delivery with Extracellular Vesicles" International Journal of Molecular Sciences 25, no. 19: 10401. https://doi.org/10.3390/ijms251910401