Shells of compacted DNA as nanocontainers transporting proteins in multiplexed delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cell Biology

Background:

• Polyethyleneimine (PEI) is known to compact DNA into various structures.
• Mannose-grafted PEI (PEIm) forms unique ~100 nm DNA spheroids resembling thin-walled shells.

Purpose of the Study:

• Investigate the mechanism behind PEIm-mediated DNA compaction into shell structures.
• Develop a method to co-deliver proteins and DNA into cells using these nanocontainers.

Main Methods:

• Dynamic Light Scattering (DLS)
• Atomic Force Microscopy (AFM)
• Transmission Electron Microscopy (TEM)
• Force Spectroscopy

Main Results:

• BSA proteins were successfully encapsulated within PEIm-DNA shells without altering shell architecture.
• Shell assembly is governed by micelle-like partitioning of hydrophobic and hydrophilic layers.
• Co-transfection of DNA and BSA into HEK293T cells was significantly enhanced using BSA-laden DNA shells.
• Evidence of BSA release in the nucleus and secretory granules was observed.

Conclusions:

• PEIm-DNA nanocontainers offer an efficient method for co-delivering proteins and DNA into cells.
• This platform is rapid, DNA sequence-independent, and adaptable for various proteins.
• Potential applications include theranostics, multiplexed co-delivery, and gene editing.