Novel functionalized nanoparticles for tumor-targeting co-delivery of doxorubicin and siRNA to enhance cancer therapy

Human homeobox protein (Nanog) is highly expressed in most cancer cells and has gradually emerged as an excellent target in cancer therapy, owing to its regulation of cancer cell proliferation, metastasis and apoptosis. In this study, we prepared tumor-targeting functionalized selenium nanoparticles (RGDfC-SeNPs) to load chemotherapeutic doxorubicin (DOX) and Nanog siRNA. Herein, RGDfC peptide was used as a tumor-targeting moiety which could specifically bind to α v β 3 integrins overexpressed on various cancer cells. The sizes of [email protected] nanoparticles (~12 nm) were confirmed by both dynamic light scattering and transmission electron microscopy. The chemical structure of [email protected] was characterized via Fourier-transform infrared spectroscopy. The [email protected] was compacted with siRNA (anti-Nanog) by electrostatic interaction to fabricate the [email protected] /siRNA complex. The [email protected] /siRNA complex nanoparticles could efficiently enter into HepG2 cells via clathrin-associated endocytosis, and showed high gene transfection efficiency that resulted in enhanced gene silencing. The in vivo biodistribution experiment indicated that [email protected] /siRNA nanoparticles were capable of specifically accumulating in the tumor site. Furthermore, treatment with [email protected] /siRNA resulted in a more significant anticancer activity than the free DOX, [email protected] or RGDfC-SeNPs/siRNA in vitro and in vivo. In summary, this study shows a novel type of DOX and siRNA co-delivery system, thereby providing an alternative route for cancer treatment.