  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.
