Unique Surface Modification of Silica Nanoparticles with Polyethylenimine (PEI) for siRNA Delivery Using Cerium Cation Coordination Chemistry

The discovery of RNA interference (RNAi) as a naturally occurring mechanism for gene knockdown has attracted considerable attention toward the use of small interfering RNAs (siRNAs) for therapeutic purposes. The main obstacles of harnessing siRNAs a drugs are their inefficient delivery to cells and off-target effect making clinical applications very challenging. The positively charged, branched 25 kDa polyethylenirnine (b-PEI) polymer is widely regarded as one of the most efficient nonviral commercially available transfection agents. However, it has also been shown that 25 kDa b-PEI is highly cytotoxic and can readily lead to cell death. In this specific context, this study presents the preparation and characterization of innovative 25 kDa b-PEI-decorated polycationic silica nanopartides (SiO2 NPs) for cellular siRNA delivery and subsequent gene silencing. A new method of b-PEI attachment onto the SiO2 NP surface has been developed that makes use of cerium(III) cations (Ce3+), a lanthanide group element, as an effective noncovalent inorganic linker between both polyNH(2)-SiO2 nanoparticle (SPA NPs) surface and polycationic 25 kDa b-PEI polymer. Two resulting novel SPA-Ce-PEI NPs consist of similar amounts of b-PEI, while possessing different amounts of Ce3+. Various analytical techniques (TEM, DLS, zeta potential, ICP-AES, and TGA) have been used to deeply characterize NPs physicochemical qualities. The observed results of Ce3+-dependent gene silencing and cytotoxic activities led us to conclusions about the role of Ce3+-N bonding during the chemical attachment of the 25 kDa b-PEI shell onto the NP surface.