Comparing gene silencing and physiochemical properties in siRNA bound cationic star-polymer complexes.

Comparing gene silencing and physiochemical properties in siRNA bound cationic star-polymer complexes.
Biomacromolecules. 2016 Oct 6;:
Authors: Dearnley M, Reynolds NP, Cass P, Wei X, Shi S, Mohammed AA, Le T, Gunatillake P, Tizard ML, Thang SH, Hinton TM
Abstract
The translation of siRNA into clinical therapies has been significantly delayed by issues surrounding the delivery of naked siRNA to target cells. Here we investigate siRNA delivery by cationic acrylic polymers developed by Reversible Addition Fragmentation chain Transfer (RAFT) mediated free radical polymerization. We investigated cell uptake and gene silencing of a series of siRNA-star polymer complexes both in the presence and absence of a protein "corona". Using a multidisciplinary approach including quantitative nanoscale mechanical-atomic force microscopy, dynamic light scattering and nanoparticle tracking analysis we have characterized the nanoscale morphology, stiffness and surface charge of the complexes with and without the protein corona. This is one of the first examples of a comprehensive physiochemical analysis of siRNA-polymer complexes being performed alongside in vitro biological assays, allowing us to describe a set of desirable physical features that promote gene silencing in cationic polymer complexes. Multi-faceted studies such as this will improve our understanding of structure-function relationships in nano-therapeutics, facilitating the rational desi...

Source: Biomacromolecules - October 5, 2016 Category: Biochemistry Authors: Dearnley M, Reynolds NP, Cass P, Wei X, Shi S, Mohammed AA, Le T, Gunatillake P, Tizard ML, Thang SH, Hinton TM Tags: Biomacromolecules Source Type: research