Layer-by-Layer siRNA Particle Assemblies for Localized Delivery of siRNA to Epithelial Cells through Surface-Mediated Particle Uptake

Localized delivery of small interfering RNA (siRNA) is a promising approach for spatial control of cell responses at biomaterial interfaces. Layer-by-layer (LbL) assembly of siRNA with cationic polyelectrolytes has been used in film and nanoparticle vectors for transfection. Herein, we combine the ability of particles to efficiently deliver siRNA with the ability of film polyelectrolyte multilayers to act locally. LbL particles were prepared with alternating layers of poly(L-arginine) and siRNA and capped with hyaluronic acid. Negatively charged LbL particles were subsequently assembled on the poly(L-lysine)-functionalized substrate to form a LbL particle-decorated surface. Cells grown in contact with the particle-decorated surface were able to survive, internalize particles, and undergo gene silencing. This work shows that particle-decorated surfaces can be engineered by using electrostatic interactions and used to deliver therapeutic payloads for cell instructive biointerfaces.

Automated summary

Localized delivery of siRNA using electrostatic interactions has been achieved by assembling siRNA with cationic polyelectrolytes to create particle-decorated surfaces, which allows for spatial control of cell responses at biomaterial interfaces. The results demonstrate that cells in contact with the particle-decorated surface can survive, internalize particles, and undergo gene silencing. This study highlights the engineering potential of particle-decorated surfaces for delivering therapeutic payloads and guiding cell responses at biointerfaces.