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Updated: Oct 1, 2025

Nanoparticle Tracking Analysis for the Quantification and Size Determination of Extracellular Vesicles
Published on: March 28, 2021
Extracellular Vesicles Mediate the Intercellular Exchange of Nanoparticles
Xian Wu1, Tang Tang1, Yushuang Wei1
1Department of Pharmaceutics, University of Minnesota, Minneapolis, MN, 55455, USA.
Nanoparticles (NPs) use intercellular exchange, involving exocytosis and re-entry, for tissue transport. Extracellular vesicles (EVs) play a significant role in this NP transport, facilitating delivery into complex tissues.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cell Biology
Background:
- Nanoparticles (NPs) require transcellular transport for therapeutic delivery into multilayered tissues.
- While NP uptake and intracellular transport are understood, NP exocytosis and re-entry (intercellular exchange) remain poorly characterized, hindering effective delivery.
- Understanding intercellular exchange is critical for advancing NP-based therapies.
Purpose of the Study:
- To develop a quantitative assay for measuring nanoparticle (NP) intercellular exchange.
- To elucidate the mechanisms of NP exocytosis and re-entry between cells.
- To investigate the role of extracellular vesicles (EVs) in NP intercellular transport.
Main Methods:
- Development of a collagen-based three-dimensional (3D) assay to quantify NP intercellular exchange.
- Distinguishing between free NP exocytosis and EV-enclosed NP transport.
- In vitro and in vivo validation of NP transport mechanisms.
Main Results:
- Nanoparticles are exocytosed either freely or enclosed within extracellular vesicles (EVs) for subsequent cell entry.
- EVs mediate a significant portion of NP intercellular exchange, crucial for transport in complex tissues.
- Freely released NPs use cell receptors for re-entry, whereas EV-enclosed NPs bypass this receptor-dependent mechanism.
Conclusions:
- A novel 3D assay enables precise quantification of NP intercellular exchange.
- Extracellular vesicles (EVs) are key mediators of nanoparticle transport between cells and into tissues.
- This research highlights the critical, previously underestimated role of EVs in nanoparticle delivery systems.
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