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The AgNPs\u2019 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 \u00b5M (2.3 \u00b5g\/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 \u00b5M (600 \u00b5g\/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 \u00b5M; 7.4 \u00b5g\/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 \u00b5M to 5.5 mM (0.6 to 600 \u00b5g\/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.<\/jats:p>","DOI":"10.3390\/pharmaceutics13010065","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T00:04:35Z","timestamp":1609977875000},"page":"65","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["New Protein-Coated Silver Nanoparticles: Characterization, Antitumor and Amoebicidal Activity, Antiproliferative Selectivity, Genotoxicity, and Biocompatibility Evaluation"],"prefix":"10.3390","volume":"13","author":[{"given":"Luc\u00eda Margarita","family":"Valenzuela-Salas","sequence":"first","affiliation":[{"name":"Facultad de Ciencias de la Salud, Universidad Aut\u00f3noma de Baja California, Tijuana 22260, Baja California, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2401-6237","authenticated-orcid":false,"given":"Alberto","family":"Blanco-Salazar","sequence":"additional","affiliation":[{"name":"Programa de Maestr\u00eda y Doctorado en Ciencias e Ingenier\u00eda (MyDCI), Facultad de Ciencias, Universidad Aut\u00f3noma de Baja California, Ensenada 22860, Baja California, Mexico"},{"name":"Escuela de Ciencias de la Salud Unidad Valle Dorado, Universidad Aut\u00f3noma de Baja California, Ensenada 22890, Baja California, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas David","family":"Perrusqu\u00eda-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Facultad de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Nequiz-Avenda\u00f1o","sequence":"additional","affiliation":[{"name":"Unidad de Medicina Experimental, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paris A.","family":"Mier-Maldonado","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Universidad Aut\u00f3noma de Baja California, Tijuana 22260, Baja California, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balam","family":"Ruiz-Ruiz","sequence":"additional","affiliation":[{"name":"Facultad de Medicina unidad los Mochis, Universidad Aut\u00f3noma de Sinaloa, Los Mochis 81223, Sinaloa, Mexico"},{"name":"Facultad de Ciencias, Universidad Aut\u00f3noma de Baja California, Ensenada 22860, Baja California, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Campos-Gallegos","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias de la Salud, Universidad Aut\u00f3noma de Occidente, Los Mochis 81223, Sinaloa, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0997-6902","authenticated-orcid":false,"given":"Mar\u00eda Evarista","family":"Arellano-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias de la Salud, Universidad Aut\u00f3noma de Occidente, Los Mochis 81223, Sinaloa, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9861-2467","authenticated-orcid":false,"given":"Juan Carlos","family":"Garc\u00eda-Ramos","sequence":"additional","affiliation":[{"name":"Escuela de Ciencias de la Salud Unidad Valle Dorado, Universidad Aut\u00f3noma de Baja California, Ensenada 22890, Baja California, 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