No abstract

brush property shared by most of these applications is the ability to regulate protein interactions and diffusion to substrates from which brushes are tethered. Hence, the exceptional protein resistance of polymer brushes enables to control their specificity of binding for biorecognition [6,7] or to promote cell adhesion, [8][9][10] whereas other brushes modulate the mechanism of adsorption and ultimate conformation of bioactive proteins. [11] In many cases, the ability of brushes to modulate protein-surface interactions and adsorption is associated with neutral brushes that do not promote strong interactions with other macromolecules.In contrast, densely charged polyelectrolyte brushes, such as those based on poly(dimethylaminoethyl methacrylate) (PDMAEMA) and poly(2-methacrylolyloxyethyltrimethylammonium iodide) (PMETAI), are expected to promote strong interactions, in particular with low isoelectric point proteins, at neutral pH, [12][13][14][15] a useful property to maximize the loading of surfaces with enzymes, for example. In addition, polycationic brushes have found application for gene delivery, owing to their ability to capture negatively charged DNA and RNA macromolecules. [16][17][18] Nanoparticles can be decorated with polycationic brushes that can capture genetic materials to be delivered upon internalization, presenting different core chemistries for imaging or to control degradation. [19,20] These nanomaterials, once loaded with oligonucleotides or plasmid DNA, can then be delivered to cells for evaluation of transfection efficiencies. [21,22] A range of different brush design parameters have been found to play crucial roles in regulating transfection efficiencies. Hence the grafting density and thickness of brushes were found to modulate the binding and infiltration of oligonucleotides and, in turn, the knockdown efficiency of siRNAs. [21] The type of buffer used to complex plasmid DNA was also found to regulate the morphology and surface density of adsorbed plasmids. [16] In turn, the brush chemistry was found to modulate the adsorption of oligonucleotides, and their rate of desorption upon internalization, through competitive binding with cytosolic macromolecules. [22] Therefore, the macromolecular structure and solution morphology of polymer brushes have been found to play important roles in regulating the adsorption and intercalation of oligonucleotides and plasmid DNA, and are proposed to control not only the complexation but also the cytosolic release of the genetic cargos. Such impact of polymer brush chemistry, structure, and morphology on macromolecular interactions is in good agreement with self-consistent field theories, scaling Polycationic brushes are attractive systems for the design of nanomaterials for gene delivery as they enable rational design of their architecture with a broad range of grafting densities, thicknesses, and chemistries. Recently, their performance for siRNA delivery is highlighted and the strong impact of their molecular architecture on RNA binding and transfecti...

Polycationic brushes are attractive systems for the design of nanomaterials for gene delivery as they enable rational design of their architecture with a broad range of grafting densities, thicknesses and chemistries. Recently, their performance for siRNA delivery was highlighted and the strong impact of their molecular architecture on RNA binding and transfection efficiency now calls for a greater understanding of the architecture of polymer brush-oligonucleotide complexes. In this study, the morphology of polymer brushes with a range of grafting densities, thicknesses and chemistry (weak polybase poly(dimethylaminoethyl methacrylate), PDMAEMA, and strong poly(2-methacrylolyloxyethyltrimethylammonium iodide), PMETAI) and their complexes with 20 base pair siRNA oligonucleotides are first investigated. These assemblies are then studied via neutron reflectometry, building first a model of brush swelling in deionised water, at three different contrasts, prior to the investigation of brush-RNA complexes. It is found that oligonucleotides infiltrate deep within the brush and alter the morphology of their most basal layer more strongly, regardless of the strength of the polybase. This understanding will enable the improved rational design of polymer brush nanostructures for gene delivery applications.