DNA Nanostructure-Programmed Cell Entry via Corner Angle-Mediated Molecular Interaction with Membrane Receptors

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cell Biology

Background:

• Deoxyribonucleic acid (DNA) nanostructures offer biomedical potential due to their ability to enter cells.
• Understanding the geometric impact on DNA nanostructure cell entry is crucial but not well-elucidated.

Purpose of the Study:

• To investigate how geometrical parameters of framework nucleic acids (FNAs) influence cellular uptake.
• To elucidate the mechanism of FNA-cell membrane interaction and internalization.

Main Methods:

• Experimental studies on the cellular uptake of three distinct FNAs (tetrahedron, triangular prism, cube).
• Utilized multiple cell lines to assess uptake efficiency.
• Employed molecular docking simulations to analyze interactions with scavenger receptors (SRs).

Main Results:

• Observed varying cellular uptake efficiencies among different FNAs across multiple cell lines.
• Identified scavenger receptors (SRs) as essential mediators for FNA cellular entry.
• Molecular docking revealed that FNA corner angles dictate SR binding and subsequent internalization.

Conclusions:

• The geometrical properties, specifically corner angles, of FNAs are critical determinants of cellular uptake.
• This research provides mechanistic insights into FNA-cell membrane interactions, crucial for designing targeted nanocarriers.
• Findings contribute to understanding virus-cell entry mechanisms and developing novel theranostic nanocarriers.