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

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 cellinstructive biointerfaces.

Modulating the Nature of Ionizable Lipids and Number of Layers in Hyaluronan-Decorated Lipid Nanoparticles for In Vitro Delivery of RNAi

“…First, the 5× HA-LNPs possess the double amount of Poly-L-Arginine as the 3× HA-LNPs. PLA is a known endosomal escape-inducing polypeptide that provides siRNA gene transfection ability to LbL-assembled nanoparticles [ 36 ]. Secondly, the likely higher stability of a multilayered system could also have an impact in the gene transfection in vitro.…”

Engineering Cell Membranes: From Extraction Strategies to Emerging Biosensing Applications

“…131 Small interference RNA (siRNA), another important class of RNA molecules, has been reported as a potential gene therapy drug due to its gene-targeting (knockdown) function. 132 To date, many effective materials, including liposomes, polymers, and peptide-conjugated systems, have been widely used for siRNA delivery. Among them, liposome vectors based on extracted cell membranes or artificial vesicles have the advantages of good stability and high transfection efficiency and have been widely employed for siRNA delivery.…”

“…Small interference RNA (siRNA), another important class of RNA molecules, has been reported as a potential gene therapy drug due to its gene-targeting (knockdown) function . To date, many effective materials, including liposomes, polymers, and peptide-conjugated systems, have been widely used for siRNA delivery.…”