Cationic polymer brush-coated bioglass nanoparticles for the design of bioresorbable RNA delivery vectors

Cationic polymer brushes are attractive coatings for the development of gene delivery vectors, owing to the simplicity via which they enable the control of a broad range of design parameters independently of each other. Indeed, brush chemistry, grafting density, thickness and nanoparticle cores (chemistry, size and shape) can be designed and controlled separately. Although some of these parameters have been investigated in the case of poly(dimethylaminoethyl methacrylate) (PDMAEMA) brushes, including grafting density and thickness, the main core studied to date with such systems has remained silica nanoparticles that display low resorption potential. In this work, we propose to make use of bioresorbable mesoporous silica nanoparticles (MSN) for the design of brush-based gene delivery systems. We synthesise a range of MSNs with varying calcium doping levels, enabling to regulate resorption. We demonstrate the growth of PDMAEMA brushes from these bioglass nanoparticles and study some of their physico-chemical properties. We demonstrate the control of brush release from these nanomaterials, through their calcium content and surface erosion. Finally, we quantify their efficacy in a siRNA knock down model. Therefore, these systems demonstrate the feasibility of designing bioresorbable brush-based gene delivery vectors.