Antiproliferative and Antitumour Effect of Nongenotoxic Silver Nanoparticles on Melanoma Models

Abstract EN

During the last 3 decades, there has been a slow advance to obtain new treatments for malignant melanoma that improve patient survival.

In this work, we present a systematic study focused on the antiproliferative and antitumour effect of AgNPs.

These nanoparticles are fully characterized, are coated with polyvinylpyrrolidone (PVP), and have an average size of 35±15 nm and a metallic silver content of 1.2% wt.

Main changes on cell viability, induction of apoptosis and necrosis, and ROS generation were found on B16-F10 cells after six hours of exposure to AgNPs (IC50=4.2 μg/mL) or Cisplatin (IC50=2.0 μg/mL).

Despite the similar response for both AgNPs and Cisplatin on antiproliferative potency (cellular viability of 53.95±1.88 and 53.62±1.04) and ROS production (20.27±1.09% and 19.50±0.35%), significantly different cell death pathways were triggered.

While AgNPs induce only apoptosis (45.98±1.88%), Cisplatin induces apoptosis and necrosis at the same rate (22.31±1.72% and 24.07±1.10%, respectively).

In addition to their antiproliferative activity, in vivo experiments showed that treatments of 3, 6, and 12 mg/kg of AgNPs elicit a survival rate almost 4 times higher (P<0.05) compared with the survival rate obtained with Cisplatin (2 mg/kg).

Furthermore, the survivor mice treated with AgNPs do not show genotoxic damage determined by micronuclei frequency quantification on peripheral blood cells.

These results exhibit the remarkable antitumour activity of a nongenotoxic AgNP formulation and constitute the first advance toward the application of these AgNPs for melanoma treatment, which could considerably reduce adverse effects provoked by currently applied chemotherapeutics.