Antitumor Activity against Human Colorectal Adenocarcinoma of Silver Nanoparticles: Influence of [Ag]/[PVP] Ratio

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.

The Infectious Bronchitis Coronavirus Pneumonia Model Presenting a Novel Insight for the SARS-CoV-2 Dissemination Route

“…Although MAPK/ERK1/2 pathways generally promote cell survival, certain circumstances such as DNA or oxidative damage function as pro-apoptotic signaling [ 42 ]. Oxidative stress and DNA damage have been described on several tumor cells exposed to Argovit AgNPs, promoting cell death by an intrinsic apoptotic pathway [ 43 , 44 ]. Thus, the apoptotic pathway could be activated on cells harboring IBV due to the virus-promoted autophagosome increase and redox damage promoted by the presence of AgNPs, leading to cell death and the inhibition of virus proliferation.…”

Treatment with Argovit® Silver Nanoparticles Induces Differentiated Postharvest Biosynthesis of Compounds with Pharmaceutical Interest in Carrot (Daucus carota L.)

“…Molecular masses of PVP K-15, K-17, and K-30 PVP (Boai NKY Pharmaceuticals Ltd., Jiaozuo, China) are 8000-12,000 kDa, 10,000-16,000 kDa, and 45,000-58,000 kDa, respectively. The morphology, zeta potential, average diameter, and thermogravimetric analysis of used silver nanoparticles have been previously reported [24].…”

“…Our research group has been working with AgNP formulations stabilized with polyvinylpyrrolidone (PVP) as coating agent. These AgNPs possess a defined (Ag)/(coating agent ratio) that contributes to their low toxicity on reference systems like Allium cepa [21], human peripheral blood erythrocytes [22] and lymphocytes [23], and mice [24,25]. The oral lethal dose study shows that the five AgNP formulations investigated in the present study are included in Category 4 (>300 to ≤ 2000 mg/Kg bodyweight) or Category 5 (>2000 to ≤ 5000 mg/Kg bodyweight) of the Globally Harmonized System of Classification and Labelling of Chemicals [24].…”

A Comparative Study of Cancer Cells Susceptibility to Silver Nanoparticles Produced by Electron Beam

“…The effect of AgNPs on tumor cells is of particular interest. The results obtained by our group for AgNPs synthesized with an electron beam and stabilized with PVP and PH allows us to consider AgNPs as potential agents for cancer therapy [ 28 , 29 ]. This study aimed to demonstrate that AgNPs formulations synthesized with an electron beam and stabilized with PVP and PH hydrolysate are promising agents as an alternative for cancer treatment.…”