Macedo, Letícia Bueno and Nogueira-Librelotto, Daniele Rubert and Mathes, Daniela and de Vargas, Josiele Melo and da Rosa, Raquel Mello and Rodrigues, Oscar Endrigo Dorneles and Vinardell, Maria Pilar and Mitjans, Montserrat and Rolim, Clarice Madalena Bueno (2021) Overcoming MDR by Associating Doxorubicin and pH-Sensitive PLGA Nanoparticles Containing a Novel Organoselenium Compound—An In Vitro Study. Pharmaceutics, 14 (1). p. 80. ISSN 1999-4923
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Abstract
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.
Item Type: | Article |
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Uncontrolled Keywords: | selenium compounds; pH-responsive nanoparticles; combination therapy; tumor cell lines; multidrug resistance (MDR) |
Subjects: | Euro Archives > Medical Science |
Depositing User: | Managing Editor |
Date Deposited: | 11 Nov 2022 04:35 |
Last Modified: | 19 Aug 2023 04:22 |
URI: | http://publish7promo.com/id/eprint/101 |