Degradable polyelectrolyte multilayers that promote the release of siRNA

Area of Science:

• Biomaterials Science
• Nanotechnology
• Molecular Biology

Background:

• Controlled release of nucleic acids is crucial for therapeutic and research applications.
• Polyelectrolyte multilayers (PEMs) offer a versatile platform for surface functionalization and material design.

Purpose of the Study:

• To design degradable polyelectrolyte-based films for controlled release of small interfering RNA (siRNA) from surfaces.
• To investigate the release kinetics and functionality of siRNA incorporated into PEMs.

Main Methods:

• Stepwise, layer-by-layer assembly of PEMs using siRNA and a hydrolytically degradable poly(β-amino ester).
• Fabrication of ultrathin films (∼50 nm) using siRNA sequences for GFP or firefly luciferase.
• Physicochemical characterization of film growth, erosion, and siRNA release profiles.
• In vitro assessment of siRNA functionality in mammalian cells.

Main Results:

• PEMs fabricated with siRNA showed linear film growth and surface-mediated siRNA release.
• siRNA release occurred in an initial burst (∼65% in 1 hour) followed by a slower phase over 23 hours, distinct from plasmid DNA release.
• Released siRNA remained intact, functional, and capable of silencing targeted protein expression in vitro.

Conclusions:

• Degradable polyelectrolyte films provide a platform for localized, controlled siRNA release from surfaces.
• The size difference between siRNA and plasmid DNA significantly influences film erosion and release profiles.
• This approach enables the development of novel research tools and delivery systems for film-coated devices.