Self-Sealing Porous Silicon-Calcium Silicate Core-Shell Nanoparticles for Targeted siRNA Delivery to the Injured Brain

摘要

A single-step procedure to simultaneously load and protect high concentrations of siRNA in porous silicon nanoparticles (pSiNPs) is presented. Treatment of pSiNPs with an aqueous solution containing siRNA and calcium chloride generates core-shell nanostructures consisting of an siRNA-loaded pSiNP core infiltrated with an insoluble shell of calcium silicate (Ca-pSiNPs). The source of silicate in the shell derives from local dissolution of the pSi matrix, and in solutions containing high concentrations of calcium (II) ion, Ca2SiO4 formation occurs primarily at the nanoparticle surface and is self-limiting. The insoluble calcium silicate shell slows the degradation of the pSiNP skeleton and prolongs delivery of the siRNA payload, resulting in more effective gene knockdown in vitro. Formation of the calcium silicate shell results in an increase in the external quantum yield of photoluminescence from the porous silicon core from 0.1 to 21 %, presumably due to the electronically passivating nature of the silicate shell. Attachment of two functional peptides that incorporate a sequence derived from the rabies virus glycoprotein (RVG) as a neuronal targeting peptide and myristoylated transportan (mTP) as a cell penetrating moiety to the Ca-pSiNPs yields a construct that shows improved gene silencing in vitro and improved delivery in vivo.