Delivery of Small Genetic Molecules through Hollow Porous Nanoparticles Silences Target Gene and in Turn Stimulates Osteoblastic Differentiation

Abstract

Nanocarriers are one of the key elements to improve the therapeutic potential of signaling molecules, including genes for the disease treatment and tissue repair. Here, a nanocarrier system is reported that delivers genetic molecule small interference RNA (siRNA) for osteoblastic stimulation. For this, a hollow form of mesoporous silica nanoshell (MSns) is designed to load and release siRNA to silence Plekho-1 gene. In particular, a pressure-induced loading method is effective in enhancing the incorporation of siRNA within a hollow space; a loading level attained ≈30% is almost three times higher than that of a non-hollow form. Furthermore, the release of siRNA from the nanocarriers is highly sustainable; continued over 18 d in a diffusion-controlled manner, in striking contrast to the rapid release (3 d) from a non-hollow form. The nanocarriers exhibit excellent cell viability, and the siRNA-nanocarrier complexes are efficiently internalized to osteoblastic cells (uptake level over 90%). The intracellular delivery suppresses the target gene Plekho-1 expression down to 20%, which in turn up-regulates the expression of osteoblast transcriptional factors (Runx2 and Smad2), demonstrating an effective gene delivery system for bone repair. Show more