RESUMO
In this study, we developed PLGA nanoparticles (NPs) as an effective carrier for 5'-Se-(phenyl)-3-(amino)-thymidine (ACAT-Se), an organoselenium compound, nucleoside analogue that showed promising antitumor activity in vitro. The PLGA NPs were prepared by the nanoprecipitation method and modified with a pH-responsive lysine-based surfactant (77KL). The ACAT-Se-PLGA-77KL-NPs presented nanometric size (around 120 nm), polydispersity index values < 0.20 and negative zeta potential values. The nanoencapsulation of ACAT-Se increased its antioxidant (DPPH and ABTS assays) and antitumor activity in MCF-7 tumor cells. Hemolysis study indicated that ACAT-Se-PLGA-77KL-NPs are hemocompatible and that 77KL provided a pH-sensitive membranolytic behavior to the NPs. The NPs did not induce cytotoxic effects on the nontumor cell line 3T3, suggesting its selectivity for the tumor cells. Moreover, the in vitro antiproliferative activity of NPs was evaluated in association with the antitumor drug doxorubicin. This combination result in synergistic effect in sensitive (MCF-7) and resistant (NCI/ADR-RES) tumor cells, being especially able to successfully sensitize the MDR cells. The obtained results suggested that the proposed ACAT-Se-loaded NPs are a promising delivery system for cancer therapy, especially associated with doxorubicin.
RESUMO
This article presents the preparation and in vitro biological activities of new 5'-arylchalcogeno-3-aminothymidine derivatives as antioxidants (inhibition of lipid peroxidation, scavenging of the free radical 2,2-diphenylpicrylhydrazyl and demonstration of a thiol peroxidase-like activity) as well as antitumoral agents against bladder carcinoma 5637. The chalcogeno-aminothymidines presented prominent activity in the tests for both biological properties, showing a direct relation with the chalcogenium atom.