Topology Determines DNA Origami Diffusion in Intestinal Mucus.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Mucosal barriers present significant challenges for nanomedicine delivery.
• Understanding nanoparticle-mucus interactions is crucial for effective drug delivery systems.

Purpose of the Study:

• To investigate the influence of nanoparticle shape and ligand patterning on mucus diffusivity using DNA origami.
• To establish design rules for developing next-generation mucus-penetrating drug delivery systems.

Main Methods:

• Utilized DNA origami to create nanostructures with varying shapes (rods, icosahedra, rectangles) and controlled ligand densities.
• Employed high-resolution single-particle tracking to systematically evaluate nanoparticle diffusion in mucus.
• Maintained identical material composition across all tested nanostructures.

Main Results:

• Nanoparticle diffusivity in mucus depends on the interplay between shape and ligand patterning, not solely on individual factors.
• Unmodified rod nanoparticles showed poor diffusion, but antibody functionalization significantly increased mobility.
• Optimal ligand density was identified for maximizing rod nanoparticle mobility in mucus.

Conclusions:

• Topology-specific optimization is essential for designing effective nanoparticle drug delivery systems.
• DNA nanotechnology provides a powerful platform for uncovering fundamental principles of nanoparticle transport in biological mucus.
• Findings guide the development of advanced nanomedicines for enhanced mucosal delivery.