Differential Surface Engineering Generates Core-Shell Porous Silicon Nanoparticles for Controlled and Targeted Delivery of an Anticancer Drug.

An approach to differentially modify the internal surface of porous silicon nanoparticles (pSiNPs) with hydrophobic dodecene and the external surface with antifouling poly- N -(2-hydroxypropyl) acrylamide (polyHPAm) as well as a cell-targeting peptide was developed. Specifically, to generate these core-shell pSiNPs, the interior surface of a porous silicon (pSi) film was hydrosilylated with 1-dodecene, followed by ultrasonication to create pSiNPs. The new external surfaces were modified by silanization with a polymerization initiator, and surface-initiated atom transfer radical polymerization was performed to introduce polyHPAm brushes. Afterward, a fraction of the polymer side chain hydroxyl groups was activated to conjugate cRGDfK─a peptide with a high affinity and selectivity for the α ν β 3 integrin receptor that is overexpressed in prostate and melanoma cancers. Finally, camptothecin, a hydrophobic anti-cancer drug, was successfully loaded into the pores. This drug delivery system showed excellent colloidal stability in a cell culture medium, and the in vitro drug release kinetics could be fine-tuned by the combination of internal and external surface modifications. In vitro studies by confocal microscopy and flow cytometry revealed improved cellular association attributed to cRGDfK. Furthermore, the cell viability results showed that the drug-loaded and peptide-functionalized nanoparticles had enhanced cytotoxicity toward a C4-2B prostate carcinoma cell line in both 2D cell culture and a 3D spheroid model.