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Article

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

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Facultad de Ciencias de la Salud, Universidad Autónoma de Baja California, Tijuana 22260, Baja California, Mexico
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Programa de Maestría y Doctorado en Ciencias e Ingeniería (MyDCI), Facultad de Ciencias, Universidad Autónoma de Baja California, Ensenada 22860, Baja California, Mexico
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Escuela de Ciencias de la Salud Unidad Valle Dorado, Universidad Autónoma de Baja California, Ensenada 22890, Baja California, Mexico
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Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico
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Unidad de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México 06720, Mexico
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Facultad de Medicina unidad los Mochis, Universidad Autónoma de Sinaloa, Los Mochis 81223, Sinaloa, Mexico
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Facultad de Ciencias, Universidad Autónoma de Baja California, Ensenada 22860, Baja California, Mexico
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Departamento de Ciencias de la Salud, Universidad Autónoma de Occidente, Los Mochis 81223, Sinaloa, Mexico
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Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia
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Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana 22260, Baja California, Mexico
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Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Ensenada 22860, Baja California, Mexico
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2021, 13(1), 65; https://doi.org/10.3390/pharmaceutics13010065
Received: 10 December 2020 / Revised: 29 December 2020 / Accepted: 30 December 2020 / Published: 7 January 2021
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
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. View Full-Text
Keywords: non-genotoxic silver nanoparticles; biocompatibility; antitumor activity; human adenocarcinoma HCT-15; amoebicidal activity; Entamoeba histolytica; antiproliferative selectivity; medium lethal dose (LD50); GHS category 5 non-genotoxic silver nanoparticles; biocompatibility; antitumor activity; human adenocarcinoma HCT-15; amoebicidal activity; Entamoeba histolytica; antiproliferative selectivity; medium lethal dose (LD50); GHS category 5
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MDPI and ACS Style

Valenzuela-Salas, L.M.; Blanco-Salazar, A.; Perrusquía-Hernández, J.D.; Nequiz-Avendaño, M.; Mier-Maldonado, P.A.; Ruiz-Ruiz, B.; Campos-Gallegos, V.; Arellano-García, M.E.; García-Ramos, J.C.; Pestryakov, A.; Villarreal-Gómez, L.J.; Toledano-Magaña, Y.; Bogdanchikova, N. New Protein-Coated Silver Nanoparticles: Characterization, Antitumor and Amoebicidal Activity, Antiproliferative Selectivity, Genotoxicity, and Biocompatibility Evaluation. Pharmaceutics 2021, 13, 65. https://doi.org/10.3390/pharmaceutics13010065

AMA Style

Valenzuela-Salas LM, Blanco-Salazar A, Perrusquía-Hernández JD, Nequiz-Avendaño M, Mier-Maldonado PA, Ruiz-Ruiz B, Campos-Gallegos V, Arellano-García ME, García-Ramos JC, Pestryakov A, Villarreal-Gómez LJ, Toledano-Magaña Y, Bogdanchikova N. New Protein-Coated Silver Nanoparticles: Characterization, Antitumor and Amoebicidal Activity, Antiproliferative Selectivity, Genotoxicity, and Biocompatibility Evaluation. Pharmaceutics. 2021; 13(1):65. https://doi.org/10.3390/pharmaceutics13010065

Chicago/Turabian Style

Valenzuela-Salas, Lucía M., Alberto Blanco-Salazar, Jesús D. Perrusquía-Hernández, Mario Nequiz-Avendaño, Paris A. Mier-Maldonado, Balam Ruiz-Ruiz, Verónica Campos-Gallegos, María E. Arellano-García, Juan C. García-Ramos, Alexey Pestryakov, Luis J. Villarreal-Gómez, Yanis Toledano-Magaña, and Nina Bogdanchikova. 2021. "New Protein-Coated Silver Nanoparticles: Characterization, Antitumor and Amoebicidal Activity, Antiproliferative Selectivity, Genotoxicity, and Biocompatibility Evaluation" Pharmaceutics 13, no. 1: 65. https://doi.org/10.3390/pharmaceutics13010065

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