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.

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.

Nanomaterials quickly evolve to produce safe and effective biomedical alternatives, mainly silver nanoparticles (AgNPs). The AgNPs’ antibacterial, antiviral, and antitumor properties convert them into a recurrent scaffold to produce new treatment options. This work reported the full characterization of a highly biocompatible protein-coated AgNPs formulation and their selective antitumor and amoebicidal activity. The protein-coated AgNPs formulation exhibits a half-inhibitory concentration (IC50) = 19.7 µM (2.3 µg/mL) that is almost 10 times more potent than carboplatin (first-line chemotherapeutic agent) to inhibit the proliferation of the highly aggressive human adenocarcinoma HCT-15. The main death pathway elicited by AgNPs on HCT-15 is apoptosis, which is probably stimulated by reactive oxygen species (ROS) overproduction on mitochondria. A concentration of 111 µM (600 µg/mL) of metallic silver contained in AgNPs produces neither cytotoxic nor genotoxic damage on human peripheral blood lymphocytes. Thus, the AgNPs formulation evaluated in this work improves both the antiproliferative potency on HCT-15 cultures and cytotoxic selectivity ten times more than carboplatin. A similar mechanism is suggested for the antiproliferative activity observed on HM1-IMSS trophozoites (IC50 = 69.2 µM; 7.4 µg/mL). There is no change in cell viability on mice primary cultures of brain, liver, spleen, and kidney exposed to an AgNPs concentration range from 5.5 µM to 5.5 mM (0.6 to 600 µg/mL). The lethal dose was determined following the OECD guideline 420 for Acute Oral Toxicity Assay, obtaining an LD50 = 2618 mg of Ag/Kg body weight. All mice survived the observational period; the histopathology and biochemical analysis show no differences compared with the negative control group. In summary, all results from toxicological evaluation suggest a Category 5 (practically nontoxic) of the Globally Harmonized System of Classification and Labelling of Chemicals for that protein-coated AgNPs after oral administration for a short period and urge the completion of its preclinical toxicological profile. These findings open new opportunities in the development of selective, safe, and effective AgNPs formulations for the treatment of cancer and parasitic diseases with a significant reduction of side effects.

Amoebiasis is the second leading cause of death worldwide associated with parasitic disease and is becoming a critical health problem in low-income countries, urging new treatment alternatives. One of the most promising strategies is enhancing the redox imbalance within these susceptible parasites related to their limited antioxidant defense system. Metal-based drugs represent a perfect option due to their extraordinary capacity to stabilize different oxidation states and adopt diverse geometries, allowing their interaction with several molecular targets. This work describes the amoebicidal activity of five 2-(Z-2,3-diferrocenylvinyl)-4X-4,5-dihydrooxazole derivatives (X = H (3a), Me (3b), iPr (3c), Ph (3d), and benzyl (3e)) on Entamoeba histolytica trophozoites and the physicochemical, experimental, and theoretical properties that can be used to describe the antiproliferative activity. The growth inhibition capacity of these organometallic compounds is strongly related to a fine balance between the compounds’ redox potential and hydrophilic character. The antiproliferative activity of diferrocenyl derivatives studied herein could be described either with the redox potential, the energy of electronic transitions, logP, or the calculated HOMO–LUMO values. Compound 3d presents the highest antiproliferative activity of the series with an IC50 of 23 µM. However, the results of this work provide a pipeline to improve the amoebicidal activity of these compounds through the directed modification of their electronic environment.