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Multimodal Analytical Platform on a Multiplexed Surface Plasmon Resonance Imaging Chip for the Analysis of Extracellular Vesicle Subsets
Published on: March 17, 2023
Universal Microfluidic Platform for Multifunctional Surface Modification of Small Extracellular Vesicles
Yanhang Hong1, Huitao Zhang1, Lin Zeng1
1State Key Laboratory of Biomedical Imaging Science and System, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Engineered small extracellular vesicles (sEVs) overcome delivery limitations using a novel microfluidic device for targeted therapies. This universal surface engineering strategy enhances sEV biocompatibility and targeting capabilities for clinical applications.
Area of Science:
- Biotechnology
- Nanotechnology
- Materials Science
Background:
- Small extracellular vesicles (sEVs) are promising drug delivery vehicles due to their biocompatibility.
- Clinical translation of sEVs is hindered by donor cell source variability and poor targeting efficiency.
- Current engineering methods for sEVs are often inefficient and donor-dependent.
Purpose of the Study:
- To develop a universal surface engineering strategy for small extracellular vesicles (sEVs).
- To create a microfluidic device (ExoSE) for efficient lipid anchoring and ligand conjugation onto sEVs.
- To enhance the targeting capabilities and therapeutic potential of sEVs.
Main Methods:
- Developed the sEV Surface-Engineering (ExoSE) microfluidic device with nanofluidic and microfluidic modules.
- Utilized mechanoporation via nanochannels for efficient functionalized lipid insertion into sEV membranes.
- Employed optimized chemical reactions in a mixing module for rapid covalent attachment of targeting ligands.
Main Results:
- Achieved high lipid incorporation efficiencies (>97%) for sEVs from different sources.
- Demonstrated a 3- to 6-fold increase in ligand binding per sEV using NanoFCM analysis.
- Engineered sEVs showed enhanced in vitro transmembrane transport, glioma spheroid infiltration, and specific targeting of breast cancer cells (77.8% specificity).
- In vivo studies confirmed improved brain accumulation of engineered sEVs with no significant toxicity.
Conclusions:
- The ExoSE device provides a universal, scalable, and efficient platform for engineering sEVs.
- This strategy overcomes donor cell dependency and enhances targeting specificity for precision therapeutics.
- Engineered sEVs hold significant potential for advanced clinical applications in targeted drug delivery.
