Amorphous silica nanoparticles: new therapeutic approach for drug delivery in Triple Negative Breast Cancer

Abstract

Triple Negative Breast Cancer(TNBC) is a heterogeneous group of tumors with difficult clinical management. Nanotechnology represents a strategy to improve current therapies. The aim of this work is to develop amorphous silica nanoparticles(SiNPs) as carriers for drugs involved in TNBC. Synthesis, physicochemical characterization and evaluation on the viability of TNBC cell lines of two SiNPs formulations were performed: amino-functionalized SiNPs(Si@NH2 ) and SiNPs modified with folic acid(FA) (Si@FA). Modified Stöber process was applied to obtain Si@NH2 . FA was covalently linked (Si@FA). Characterization was performed by FTIR and DLS to determine hydrodynamic diameter(Hd). Viability assays by crystal violet staining were performed in human MDA-MB-231, murine 4T1 TNBC cell lines and in non-malignant murine breast HC11 cells (10 - 500 μg/mL SiNPs, 24 h). Reactive oxygen species (ROS) generation was determined by DCDCDHF assay in MDA-MB-231 cells (500 µg/mL SiNPs). A pilot in vivo assay was conducted in mice to evaluate SiNPs acute toxicity: 30 mg/kg of Si@NH2 , Si@FA or control were administered weekly for 1 month. FTIR spectra confirmed functionalization with NH2 and FA; Hd resulted as 643.7 nm and 600.0 nm respectively. Si@FA displayed a significant reduction of the viability of MDA-MB-231 and 4T1 TNBC cells. Si@NH2 decreased 4T1 cell viability (p<0.001) although no effect was found for MDA-MB-231 cells at any of the concentrations tested. Both NPs increased ROS production with respect to control (Si@FA: p<0.001; Si@NH2 : p<0.01) and between them (p<0.001). Regarding to HC11 cells, NPs had no effect on viability. The observation of the internal organs of the animals showed no macroscopic alterations; no changes in hematocrit, behavior and body weight were observed. Altogether, these results suggest that Si@FA could be a promising nanotechnology for TNBC treatment. Further studies are in course to evaluate their effects in combination with conventional drugs.