Encapsulation of Small Extracellular Vesicles into Selectively Disassemblable Shells of PEGylated Metal-Phenolic...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cell Biology

Background:

• Small extracellular vesicles (sEVs) are crucial for intercellular communication and hold promise as drug delivery vehicles and diagnostic tools.
• Current methods for isolating and storing sEVs often compromise their structural and functional integrity due to lipid membrane disruption, protein denaturation, and nucleic acid degradation.
• Effective preservation strategies are needed to overcome these limitations for clinical applications.

Purpose of the Study:

• To develop a novel surface functionalization strategy for protecting small extracellular vesicles (sEVs) during processing and storage.
• To create selectively disassemblable protective shells for sEVs that maintain their surface integrity and functionality post-storage.
• To investigate methods for reducing cold-chain requirements and transportation costs for sEV-based therapeutics and diagnostics.

Main Methods:

• Developed a one-step surface functionalization strategy to encapsulate single sEVs within metal-phenolic networks (MPNs).
• Post-modified the MPN shells with poly(ethylene glycol) (PEG) to enhance colloidal stability and provide protection.
• Investigated various triggers (pH adjustment, competitive chelation, redox reactions) for the selective disassembly of the MPN shell.

Main Results:

• Successfully created PEGylated MPN shells that enhance the colloidal stability of sEVs.
• Demonstrated that the MPN shells effectively protect sEVs against harsh storage conditions.
• Showcased the selective and rapid disassembly of the MPN shell using multiple triggers, allowing sEV recovery without compromising integrity or function.
• Validated the potential to reduce cold-chain dependency and transportation costs.

Conclusions:

• The developed surface functionalization strategy using disassemblable MPN shells offers a robust method for preserving sEV integrity and function.
• This approach addresses key challenges in sEV processing and storage, paving the way for more stable and accessible sEV-based applications.
• The selective disassembly mechanism provides versatile recovery options, enhancing the adaptability of this technology for diverse therapeutic and diagnostic uses.