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[This corrects the article DOI: 10.1039/C5RA02374B.].
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The wide application of silver nanoparticles (AgNPs) has pointed out the need to evaluate their potential risk and toxic effects on human health. Herein, the cytotoxic effects of Argovit™ AgNPs were evaluated on eight cancer cell lines. Further cytotoxic studies were performed in gynecological cancer cell lines from cervical (HeLa) and breast (MDA-MB-231 and MCF7) cancer. In both cases, the half maximal inhibitory concentration (IC50) of AgNPs produced the formation of reactive oxygen species (ROS) after 24 h of incubation, but it was not statistically significant compared with untreated cells. However, HeLa, MDA-MB-231, and MCF7 cells treated with the maximal IC of AgNPs induced the formation of ROS either at 12 or 24 h of incubation. Genotoxicity achieved by comet assay in HeLa, MDA-MB-231, and MCF7 cells revealed that exposure to IC50 of AgNPs does not induced noticeable DNA damage in the cells. However, the IC of AgNPs provoked severe DNA damage after 12 and 24 h of exposure. We conclude that, Argovit (polyvinylpyrrolidone-coated AgNPs) induce a cytotoxic effect in a time and dose-dependent manner in all the eight cancer cell lines tested. Nevertheless, the genotoxic effect is mainly restricted by the concentration effect. The results contribute to explore new therapeutic applications of AgNPs for malignances in murine models and to study in deep the cytotoxic and genotoxic effects of AgNPs in healthy cells at the surrounding tissue of the neoplasia.
Assuntos
Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Apoptose/efeitos dos fármacos , Neoplasias da Mama , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Dano ao DNA , Relação Dose-Resposta a Droga , Feminino , Humanos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias do Colo do ÚteroRESUMO
This work takes advantage of the transformation of lidocaine hydrochloride into deep-eutectic solvents (DESs) - ionic liquid analogues - to incorporate polymerizable counterparts into DESs, such that polymer-drug complexes are synthesized by free-radical frontal polymerization without the use of a solvent. DESs are formed through hydrogen bonding of an ammonium salt with a hydrogen-bond donor (HBD). It is demonstrated that lidocaine hydrochloride - as the ammonium salt - is able to form DESs with acrylic acid and methacrylic acid. The properties of DESs allow frontal polymerization in the bulk with full conversion achieved in a one-pot synthesis, yielding monoliths of polymers loaded with a high concentration of drug. In in vitro experiments, the sustained release of the drug takes place in a controlled manner triggered by the pH, ionic strength and solubility of the drug in the medium. Such control is owed to the swelling of polymers as well as to the specific interactions between the drug and the polymers already established in the DES precursor. Finally, it is noteworthy that different monomers (such as HBD) and crosslinkers can be used, thus expanding the possibilities of drug delivery systems for transdermal technologies by exploiting the DES chemistry.