Estudo in vitro da efetividade antitumoral das nanopartículas poliméricas de quitosana carreadoras de Doxorrubicina revestidas com ácido hialurônico no tratamento de câncer de mama triplo-negativo

Abstract

The high frequency of metastatic recurrence, development of drug resistance to tumor cells and systemic side effects to conventional chemotherapy are the main obstacles to efficient treatment against triple negative breast cancer. To optimize drug delivery and evaluate its antitumor activity in a drug delivery system (DDS), the present study used chitosan nanoparticles (ChiNP) coated with hyaluronic acid (HA) and encapsulated with Doxorubicin (DOX). For this purpose, cell viability assays in tumor (4T1) and non-tumor cell lines (RAW264-7) using MTT (3-(4,5-Dimethylthiazol-2-yl) at 24-72 hours, as well as investigation of cell death by Annexin/PI in 24-48 hours and cell internalization were performed. The ChiNPs were internalized by tumor cells (4T1) showing the same fluorescence pattern in 24 h and 48 h. All the tested concentrations of the nanoparticles showed to always decrease the cell viability of 4t1 cells (p<0.05) in relation to untreated cells (DMEM) and DOX, highlighting that the concentration of 0.03uM was able to reach THE IC50 in the time of 72 hours. Interestingly, at this concentration in the time of 72 hours, there was an increase in viability in non-tumor cells (RAW264-7). When analyzing the results of cell death, it was observed that there was an increase in late apoptosis when treating all 4T1 cells with all concentrations used (p<0.05) in the time of 48 hours. These results show that ChiNPs containing DOX and coated with HA were able to induce a decrease in cell viability and consequently increase tumor cell apoptosis (4T1).