Nanobiotecnologia aplicada à oncologia

Abstract

Cancer cells demonstrate the ability for uncontrolled division and to escaping programmed cell death. There are several classes of compounds for the treatment of cancer, and in many cases only a small fraction of the drug dose reaches the tumor site, which reduces therapeutic efficiency and increases systemic toxicity. Furthermore, cancer cells exhibit resistance mechanisms. In cytotoxicity studies, nanoparticle carriers are often more effective against cancer cells than the corresponding free drug. Methotrexate (MTX) is a structural analog of folic acid that inhibits the action of the dihydrofolate reductase (DHFR) enzyme, and is commonly used in the treatment of tumors. However, it can cause side effects and the cancer cells can develop resistance. Obtaining MTX-containing nanostructured formulations can lessen the unwanted effects and maximize the therapeutic effect. To increase the encapsulation of the drug in aqueous suspensions of lipid-core nanocapsules a derivative was synthesized, diethyl ester of methotrexate (MTX(OEt)2). This study aimed to perform the in vitro evaluation of the action of lipid-core nanocapsules containing MTX(OEt)2 and the comparison with the action of the free substance in solution. For this evaluation, five tumor cell lines were used. It was observed cytotoxicity and inhibition of cell proliferation associated with treatments. Using flow cytometry analysis, it was observed that apoptosis increased in cells treated with the nanoformulation. Additionaly, by real-time PCR analysis, changes in the expression profile of genes related to apoptosis were detected. The tests used in the study complemented each other and were effective in determining responses to treatments. The MTX(OEt)2 nanoformulation demonstrated the ability to improve the in vitro antitumor effect of the compound.