Amorphous Silica Nanoparticles: Novel Chemotherapeutic Option For Triple Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors with difficult clinical management, due the lack of response to current available therapies for other BC tumors. Nanotechnology represents a strategy to obtain the selective delivery of drugs to cancer cells, thus reducing their adverse effects and increasing their efficacy. The aim of this work was to develop amorphous silica nanoparticles (SiNPs) containing folic acid (FA) as active targeting agent to obtain biocompatible carriers for drugs involved in TNBC. Modified Stöber process was applied to synthesize the amino-functionalized SiNP Si@NH2 employing 3-aminopropyltriethoxiilane (APTES) as source of –NH2 group. Then, folic acid (FA) was covalently linked to Si@NH2 obtaining Si@FA. FTIR spectra confirmed functionalization with NH2 and FA. DLS and TEM micrographs revealed monodisperse spherical shape for both SiNPs, with biocompatible sizes. Both SiNPs reduced the viability of TNBC MDA-MB-231 and 4T1 cell lines (p < 0.001; crystal violet assay) and Si@FA did not affect the growth of the mammary non-malignant HC11 cells. In addition, Si@FA induced ROS generation (p < 0.01; DCDCDHF assay) and displayed anti-proliferative and subsequently pro-apoptotic effects in MDA-MB-231 cells (p < 0.001; flow cytometry with PI-Annexin V staining). No effect was observed in the ROS generation and cell cycle of HC11 cells after Si@FA treatment. Moreover, SiNPs reduced TNBC cell migration (p < 0.001; wound healing assay) and did not affect HC11 motility. Finally, none of SiNPs caused signs of sub-acute toxicity in mice administered at 30 mg/kg over a month such as a decrease in body weight, alterations in the hematocrit and changes in the histology of spleen, brain, heart, liver, lung and kidney of the animals. In conclusion, these nanosystems displayed intrinsic antitumor activity without causing toxic in vivo effects, resulting in a promising therapeutic alternative for TNBC