Highly Stable RNA Capture by Dense Cationic Polymer Brushes for the Design of Cytocompatible, Serum-Stable SiRNA Delivery Vectors

• Published in: Biomacromolecules 2018-02, Vol.19 (2), p.606-615
• Main Authors: Li, Danyang, Sharili, Amir S, Connelly, John, Gautrot, Julien E
• Format: Article
• Language: English
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/acs.biomac.7b01686

The high density of polymer brushes confers to these coatings unique physicochemical properties, in particular for the regulation of biomolecular interaction and the design of highly selective coatings for biosensors and protein patterning. Here, we show that high density poly­(dimethylaminoethyl methacrylate) cationic polymer brushes enable the stable uptake of high levels of oligonucleotides. This is proposed to result from the high degree of crowding and associated increase in entropic driving force for the binding of polyelectrolytes such as nucleic acid molecules. We further demonstrate the ease with which such coatings allow the design of highly structured nanomaterials for siRNA delivery using block copolymer-brush-based nanoparticles that allow the protection of oligonucleotides by a protein-resistant outer block. In particular, these nanomaterials display a high serum stability and low cytotoxicity while retaining excellent knock down efficiencies. Polymer brush-based nanomaterials therefore appear particularly attractive for the rational design of a new generation of high performance theranostics and RNA delivery probes.