Abstract
Silver nanoparticles (AgNPs) not only have shown remarkable results as antimicrobial and antiviral agents but also as antitumor agents. This work reports the complete characterization of five polyvinylpyrrolidone-coated AgNP (PVP-AgNP) formulations, their cytotoxic activity against human colon tumor cells (HCT-15), their cytotoxic effect on primary mouse cultures, and their lethal dose on BALB/c mice. The evaluated AgNP formulations have a composition within the ranges Ag: 1.14–1.32% w/w, PVP: 19.6–24.5% and H2O: 74.2–79.2% with predominant spherical shape within an average size range of 16–30 nm according to transmission electron microscopy (TEM). All formulations assessed increase mitochondrial ROS concentration and induce apoptosis as the leading death pathway on HCT-15 cells. Except for AgNP1, the growth inhibition potency of AgNP formulations of human colon tumor cancer cells (HCT-15) is 34.5 times higher than carboplatin, one of the first-line chemotherapy agents. Nevertheless, 5–10% of necrotic events, even at the lower concentration evaluated, were observed. The cytotoxic selectivity was confirmed by evaluating the cytotoxic effect on aorta, spleen, heart, liver, and kidney primary cultures from BALB/c mice. Despite the cytotoxic effects observed in vitro, the lethal dose and histopathological analysis showed the low toxicity of these formulations (all of them on Category 4 of the Globally Harmonized System of Classification and Labelling of Chemicals) and minor damage observed on analyzed organs. The results provide an additional example of the rational design of safety nanomaterials with antitumor potency and urge further experiments to complete the preclinical studies for these AgNP formulations.
Highlights
The urgent need to find new effective and selective antitumor agents has found in nanotechnology a niche of opportunity and a growing field of research [1,2,3]
AgNP formulations were analyzed by transmission electron microscopy (TEM), UV-vis, DLS, and TGA
We present the complete characterization of five PVP-AgNP formulations with composition within the range Ag: 1.14–1.32% w/w, PVP: 19.6–24.5%, and H2 O: 74.2–79.2%
Summary
The urgent need to find new effective and selective antitumor agents has found in nanotechnology a niche of opportunity and a growing field of research [1,2,3]. In this field, silver nanoparticles have been one of the most studied systems [4,5,6,7]. Pharmaceutics 2021, 13, 1000 agent on selective cytotoxicity, identifying that the more stable the binding of the metallic surface with the coating agent, the lower its toxicity [8,11,12,13,14]. The metallic content/coating agent ratio plays a significant role in the cytotoxic and genotoxic response of AgNPs [18,19,20,21]
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