New Protein-Coated Silver Nanoparticles: Characterization, Antitumor and Amoebicidal Activity, Antiproliferative Selectivity, Genotoxicity, and Biocompatibility Evaluation

Abstract

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.

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

“…Interestingly, even with the significant accumulation in the tissue, minimal damage was observed. The lack of damage could be attributed to the considerable amount of coating agent, enhanced by its high clearance rate, as we have shown in previous works [18,21,[64][65][66][67]. These features definitely contribute to the wide therapeutic window found for the five formulations assessed in this work.…”

“…However, we recently showed that the coating agent selection is not the only thing you need to worry about. The metallic content/coating agent ratio plays a significant role in the cytotoxic and genotoxic response of AgNPs [ 18 , 19 , 20 , 21 ].…”

“…The aforementioned substantially contributes to Argovit ® formulation specificity against pathogens and malignant cells with neither cytotoxic nor genotoxic damage on healthy cells [ 19 , 20 ]. By using another coating agent, in this case protein, but preserving the [Ag]/[coating agent] ratio used in the previous formulation, we found that the effectiveness as an antitumor and antiparasitic agent with high selectivity and little toxicity for BALB mice/c is similar [ 21 ].…”

AgNPs Argovit™ Modulates Cyclophosphamide-Induced Genotoxicity on Peripheral Blood Erythrocytes In Vivo

“…This work investigated the genotoxic potential of the commercially available Argovit™ AgNP formulation on BALB/c mice. This formulation has shown remarkable results as an antiviral [ 13 , 14 , 34 , 35 ], antimicrobial [ 36 , 37 , 38 , 39 , 40 ], and growth promoter of commercially relevant crops [ 41 , 42 ] with very low cytotoxic [ 17 ] and phytotoxic [ 18 ] damages. For the purposes of the study, we orally administered a daily dose of 6 mg/kg of AgNPs for three consecutive days and continued the observation for five more days.…”

“…A new question arises: do AgNPs serve as adjuvants for CP? The antiproliferative activity of Argovit™ AgNPs against several human tumor cell lines has been previously reported [ 40 , 61 ]. Therefore, this suggests that the combination of AgNPs + CP could behave as a potent antiproliferative agent, significantly decreasing the genotoxic damage induced by CP potentially attributed to the action of AgNPs.…”