Multifunctional, self-assembling anionic peptide-lipid nanocomplexes for targeted siRNA delivery.

Multifunctional, self-assembling anionic peptide-lipid nanocomplexes for targeted siRNA delivery.
Biomaterials. 2014 Jun 28;
Authors: Tagalakis AD, Lee DH, Bienemann AS, Zhou H, Munye MM, Saraiva L, McCarthy D, Du Z, Vink CA, Maeshima R, White EA, Gustafsson K, Hart SL
Abstract
Formulations of cationic liposomes and polymers readily self-assemble by electrostatic interactions with siRNA to form cationic nanoparticles which achieve efficient transfection and silencing in vitro. However, the utility of cationic formulations in vivo is limited due to rapid clearance from the circulation, due to their association with serum proteins, as well as systemic and cellular toxicity. These problems may be overcome with anionic formulations but they provide challenges of self-assembly and transfection efficiency. We have developed anionic, siRNA nanocomplexes utilizing anionic PEGylated liposomes and cationic targeting peptides that overcome these problems. Biophysical measurements indicated that at optimal ratios of components, anionic PEGylated nanocomplexes formed spherical particles and that, unlike cationic nanocomplexes, were resistant to aggregation in the presence of serum, and achieved significant gene silencing although their non-PEGylated anionic counterparts were less efficient. We have evaluated the utility of anionic nanoparticles for the treatment of neuronal diseases by administration to rat brains of siRNA to BACE1, a key enzym...

Source: Biomaterials - June 28, 2014 Category: Materials Science Authors: Tagalakis AD, Lee DH, Bienemann AS, Zhou H, Munye MM, Saraiva L, McCarthy D, Du Z, Vink CA, Maeshima R, White EA, Gustafsson K, Hart SL Tags: Biomaterials Source Type: research