Polysaccharide-Polyplex Nanofilm Coatings Enhance Nanoneedle-Based Gene Delivery and Transfection Efficiency

Area of Science:

• Biomaterials Science
• Nanotechnology
• Gene Therapy

Background:

• Non-viral vectors offer safer nucleic acid delivery alternatives.
• Nanoneedles and nanostructures enable surface-mediated delivery.
• Polysaccharide-based polyplex nanofilms show potential for enhanced transfection.

Purpose of the Study:

• To investigate the synergistic combination of nanoneedles and polysaccharide-polyplex nanofilms for nucleic acid delivery.
• To assess the impact of different polyplex-polyelectrolyte nanofilm combinations on transfection efficiency.
• To elucidate the mechanism of enhanced transfection, specifically examining the role of CD44 receptor interactions.

Main Methods:

• Fabrication of nanoneedle-polysaccharide-polyplex nanofilms.
• Assessment of transfection efficiency using various polyanions and nanostructure designs.
• In vitro and cardiac tissue transfection studies.
• Investigation of CD44 receptor involvement.

Main Results:

• Synergistic combination of nanoneedles and nanofilms significantly enhanced transfection efficiency compared to polyplexes in suspension.
• Polysaccharide-based polyanions, not just hyaluronic acid, improved transfection.
• Enhanced transfection was independent of CD44 receptor interactions.
• Nanoneedles increased nanofilm transfection efficiency on cardiac tissue.
• High in vitro transfection was observed with nanostructures maximizing cell-substrate interface area.
• The system achieved high transfection with significantly lower nucleic acid amounts.

Conclusions:

• Surface-mediated transfection using nanoneedle-polysaccharide-polyplex nanofilms is an efficient and safe method for nucleic acid delivery.
• This approach requires substantially less nucleic acid compared to standard transfection methods.
• Findings broaden the scope of polyelectrolyte combinations for non-viral vector development and potential clinical applications.