Highly Efficient siRNA Delivery from Core-Shell Mesoporous Silica Nanoparticles with Multifunctional Polymer Caps

TL;DR

This paper introduces a highly efficient siRNA delivery system using core-shell mesoporous silica nanoparticles capped with a multifunctional polymer, achieving high loading, controlled release, and effective gene silencing in cells.

Contribution

The study presents a novel siRNA delivery platform combining porous silica nanocarriers with a modular polymer cap, enhancing loading capacity and transfection efficiency.

Findings

Up to 380 microg/mg siRNA loading capacity.

80% siRNA release within 24 hours.

90% gene knock-down in cell experiments.

Abstract

A new general route for siRNA delivery is presented combining porous core-shell silica nanocarriers with a modularly designed multifunctional block copolymer. Specifically, the internal storage and release of siRNA from mesoporous silica nanoparticles (MSN) with orthogonal core-shell surface chemistry was investigated as a function of pore-size, pore morphology, surface properties and pH. Very high siRNA loading capacities of up to 380 microg/mg MSN were obtained with charge-matched amino-functionalized mesoporous cores, and release profiles show up to 80% siRNA elution after 24 h. We demonstrate that adsorption and desorption of siRNA is mainly driven by electrostatic interactions, which allow for high loading capacities even in medium-sized mesopores with pore diameters down to 4 nm in a stellate pore morphology. The negatively charged MSN shell enabled the association with a block copolymer containing positively charged artificial amino acids and oleic acid blocks, which acts simultaneously as capping function and endosomal release agent. The potential of this multifunctional delivery platform is demonstrated by highly effective cell transfection and siRNA delivery into KB-cells. A luciferase reporter gene knock-down of up to 90% was possible using extremely low cell exposures with only 2.5 microg MSN containing 32 pM siRNA per 100 microL well.