The Architecture of Oligonucleotide‐Polycationic Brush Complexes – A Neutron Reflectometry Study

Abstract 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 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 deionized 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.