SÍNTESE E CARACTERIZAÇÃO DE NANOPARTÍCULA DE SÍLICA MESOPOROSA CONTENDO DOXORRUBICINA E CITARABINA PARA APLICAÇÃO BIOLÓGICA

Abstract

Cancer is a public health problem due to its high incidence and mortality. The three main types of treatment for cancer are: surgery, radiotherapy, and chemotherapy. The latter is the best-known using medications to combat cancer cells. Among the drugs used in chemotherapy treatment are cytarabine (Ara-C) and doxorubicin (Doxo), these drugs, as well as most chemotherapy drugs, do not have selectivity in cancer cells, also attacking normal cells and generating numerous side effects. An alternative to reduce these effects are nanocarriers that transport the drug to the cell, among which mesoporous silica nanoparticles (MSNs) stand out due to their characteristics, such as the possibility of carrying a greater amount of drug and being able to modify its surface. with folic acid (FA) molecules, which have high affinity for folate receptors, found in greater quantities in cancer cells. Considering the need for research aimed at reducing adverse effects caused by conventional treatments, the objective of the present work was to carry out the synthesis and characterization of MSNs containing Ara-c and Doxo chemotherapy agents and the AF driver. The characterizations were carried out by dynamic light scattering (DLS), surface area and porosity analysis using the Brunauer-Emmett-Teller (BET) method, transmission electron microscopy (TEM), absorption spectroscopy of the infrared region with Fourier Transform (FTIR), thermogravimetric analysis (TGA), elemental analysis (AE) and cytotoxicity tests carried out with the dye sulforhodamine B (in adherent strains) and MTT {[3-(4,5-dimethylthiazol-2-yl)- bromide 2,5-diphenyltetrazolium]} (in the non-adherent strain, K562). The synthesis of MSNs was confirmed by FTIR and TGA. The spherical morphology and nanometric size (~18 nm) were analyzed by TEM, BET and DLS respectively. The addition of drugs was confirmed by FTIR and quantified by AE and TGA (Ara-C ~2 and ~4.8%; Doxo ~7% respectively), as well as the addition of AF (~8 and ~5% respectively). The results obtained in the antiproliferative activity assay demonstrated that the MSNs containing the drugs showed reduced cytotoxic activity (GI50 < 4 µg/mL compared to the pure drug) with a selectivity index against non-neoplastic NIH-3T3 lines of 300 times more selective compared to K562, 200 times (U251) and 180 times (MCF7) in the MSNs@COOH-Ara-C sample and 12 times more selective compared to K562 and U251, 25 times (MCF7) in the MSNs@COOH-Doxo sample; compared to the non-neoplastic lineage J774 it was 20, 13 and 12 respectively more selective in the MSNs@COOH-Ara-C sample and 10, 10 and 21 in the MSNs@COOH-Doxo sample; and in the non-neoplastic lineage HUVEC the selectivity index was 33, 22, 20 respectively more selective compared to the MSNs@COOH-Ara-C sample. The in vivo antitumor activity showed a lower tumor volume compared to the MSNs@COOH-Ara-C (2 mg/kg) sample of 99.6% and 99.1% compared to the MSNs@COOH-Doxo sample, and inhibition of tumor growth 92.1% compared to the MSNs@COOH-Ara-C sample (2 mg/kg) and 90.7% compared to the MSNs@COOH-Doxo sample, both compared to the negative control (p < 0.01), This result is better than those obtained by Ara-C (89.5%) and Doxo (84.2%). In short, MSNs demonstrated to be promising matrices for the transport of the studied chemotherapeutic agents.