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

ACS Appl Bio Mater. 2023 Jan 16;6(1):83-92. doi: 10.1021/acsabm.2c00668. Epub 2023 Jan 4.

Abstract

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.

Keywords: drug delivery; layer-by-layer; particle surface; particle uptake; siRNA; transfection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biocompatible Materials
  • Epithelial Cells
  • Nanoparticles*
  • RNA, Small Interfering / metabolism
  • Transfection

Substances

  • RNA, Small Interfering
  • Biocompatible Materials