Synthesis of Diagnostic Silicon Nanoparticles for Targeted Delivery of Thiourea to Epidermal Growth Factor Receptor-Expressing Cancer Cells.

Abstract

The novel thiourea-functionalized silicon nanoparticles (SiNPs) have been successfully synthesized using allylamine and sulforaphane, an important anticancer drug, followed by a hydrosilylation reaction on the surface of hydrogen terminated SiNPs. Their physiochemical properties have been investigated by photoluminescence emission, Fourier transform infrared spectroscopy (FTIR) and elemental analysis. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay has been employed to evaluate in vitro toxicity in human colorectal adenocarcinoma (Caco-2) cells and human normal colon epithelial (CCD) cells. The results show significant toxicity of thiourea SiNPs after 72 h of incubation in the cancer cell line, and the toxicity is concentration dependent and saturated for concentrations above 100 μg/mL. Confocal microscopy images have demonstrated the internalization of thiourea-functionalized SiNPs inside the cells. Flow cytometry data has confirmed receptor-mediated targeting in cancer cells. This nanocomposite takes advantage of the epidermal growth factor receptor (EGFR) active targeting of the ligand in addition to the photoluminescence properties of SiNPs for bioimaging purposes. The results suggest that this novel nanosystem can be extrapolated for active targeting of the receptors that are overexpressed in cancer cells such as EGFR using the targeting characteristics of thiourea-functionalized SiNPs and therefore encourage further investigation and development of anticancer agents specifically exploiting the EGFR inhibitory activity of such nanoparticles.