Polymer-grafted porous silicon nanoparticles for enhanced siRNA delivery

Small interfering RNA (siRNA) shows promise for cancer treatment but faces biological barriers limiting its effective clinical use. To overcome these limitations and enhance siRNA’s therapeutic potential, innovative drug delivery systems are needed. Porous silicon nanoparticles (pSiNPs) are an attractive drug delivery system due to their high surface area, biodegradability, and tuneable porosity, although challenges with uncontrolled degradation, limited circulation time, and inefficient drug release remain. To address these limitations, we explored surface-initiated reversible addition-fragmentation chain transfer polymerisation to modify pSiNPs with poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and poly(oligo(ethylene glycol) methacrylate) (POEGA). PDMAEMA, an ionisable polymer with tertiary amine groups, is protonated at physiological pH and facilitates strong electrostatic interactions with negatively charged siRNA, leading to an siRNA loading capacity up to 438 ± 21 μg/mg, but resulted in burst release. The addition of the outer POEGA block, with its hydrophilic and neutral properties, resulted in a similar loading efficiency and enabled a more controlled biphasic drug release kinetics, although it reduced cellular association. Both systems successfully protected the siRNA from RNAse degradation, showed good cytocompatibility, and successful delivered siRNA targeting polo-like kinase 1 (PLK1). These results suggest that these polymer-coated pSiNPs offer a promising approach for siRNA delivery and gene therapy.