Preparation of folic acid-conjugated dendritic mesoporous silica nanoparticles for pH-controlled release and targeted delivery of a cyclometallated gold(III) complex as an antitumor agent

Abstract

The purpose of this study is to develop a targeted drug delivery system containing folic acid-conjugated dendritic amino mesoporous silica nanoparticles (DFMSNs) loaded with a cyclometallated gold(III) complex, [Au(bzpy)Cl2] (bzpy = 2-benzylpyridine), as a cytotoxic agent (Au(drug)@DFMSNs). The products, including the Au(III) complex, DFMSNs, and Au(drug)@DFMSNs, were characterized by transmission electron microscopy (TEM), field-emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), energy-dispersive X-ray (EDX), UV–Vis, 1H NMR, Fourier transformation infrared (FT-IR), Brunauer-Emmett-Teller (BET) surface area analysis, inductively coupled plasma-atomic emission spectroscopy (ICP-AES), zeta potential measurements, and dynamic light scattering (DLS). The in vitro release study in different pH conditions show that the release of the Au(III) complex from the folic acid functionalized amino mesoporous silica nanoparticles is sustained and pH dependent. The in vitro cytotoxicity test of the free Au(drug), free nanocarrier (DFMSNs), Au(drug) loaded folate-conjugated nanocarrier (Au(drug)@DFMSNs), and Au(drug) loaded nanocarrier without folate-conjugation (Au(drug)@DAMSNs) against two human cancer cell lines, including MCF-7 (human breast carcinoma cell lines) and A549 (human lung carcinoma cell lines) showed that the therapeutic efficacy of Au(drug)@DFMSNs is significantly greater than those in other compounds because the cancerous cells can uptake the folate-conjugated drug nanocarrier via folate receptors-mediated endocytosis. In addition, the different staining methods and fluorescence microscopic images were used to visualize the specific targeting ability, cellular uptake, and the anticancer activity of Au(drug)@DFMSNs and Au(drug)@DAMSNs toward the MCF-7 and A549 cancer cells. The results proved that the proposed system, Au(drug)@DFMSNs, can be used as a potent anticancer agent in targeted cancer therapies for breast cancer.