Amorphous Silica Nanoparticles: New Therapeutic Approach For Drug Delivery In Triple Negative Breast Cancer.

IBARRA A; RODRIGUEZ ALVAREZ T; ALONSO E; COLÓ GP; CLEMENTE V; FACCHINETTI, M M; CURINO.A.C.; FERRONATO MJ; AGOTEGARAY M

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC).; 2022

Sociedad Argentina de Investigación Clinica

Triple Negative Breast Cancer (TNBC) is a heterogeneous group of tumors with difficult clinical management. Nanotechnology represents a strategy to improve current cytotoxic therapies. The aim of this work is to develop amorphous silica nanoparticles (SiNPs) as potential 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 via dicyclohexylcarbodiimide (Si@FA). Characterization was performed by FTIR spectroscopy 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 probe 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@AF displayed a significant reduction of the viability of MDA-MB-231 and 4T1 TNBC cells (p ). Si@NH2 decreased 4T1 cell viability (p