Preparation and Characterization of Inulin Coated Gold Nanoparticles for Selective Delivery of Doxorubicin to Breast Cancer Cells

Abstract

A novel folate-targeted gold-based nanosystem for achieving selectivity towards folate receptor (FR) positive cells is proposed, by virtue of the fact that the FR is a molecularly targeted entity overexpressed in a wide spectrum of solid tumors. A new inulin-folate derivative (INU-FA) has been synthesized to act as coating agent for 40 nm gold nanoparticles. The obtained polymer-coated gold nanoparticles (Au@INU-FA) were characterized in terms of hydrodynamic radius, shape, zeta potential, and aqueous stability and were loaded with doxorubicin (Au@INU-FA/Doxo). Its release capability was tested in different release media. The selectivity of Au@INU-FA/Doxo system towards FRs-positive cancer cells was proved by the differences in the quantitative uptake using human breast cancer MCF7 as FR-positive cells and 16HBE epithelial as noncancer cell line. Furthermore, the folate-mediated uptake mechanism was studied by FRs-blocking experiments. On the whole Au@INU-FA/Doxo was able to be preferentially internalized into MCF7 cells proving a folate-mediated endocytosis mechanism which allowed a higher and selective cytotoxic effect towards cancer cells. The cytotoxicity profile was evaluated on both cancer and noncancer cell lines, displaying that folate-mediated targeting implied advantageous therapeutic effects, such as amplified drug uptake and increased anticancer activity towards MCF7 cancer cells.