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

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...

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Main Authors: Omar Ulises Cruz-Ramírez, Lucía Margarita Valenzuela-Salas, Alberto Blanco-Salazar, José Antonio Rodríguez-Arenas, Paris A. Mier-Maldonado, Juan Carlos García-Ramos, Nina Bogdanchikova, Alexey Pestryakov, Yanis Toledano-Magaña
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/13/7/1000
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author Omar Ulises Cruz-Ramírez
Lucía Margarita Valenzuela-Salas
Alberto Blanco-Salazar
José Antonio Rodríguez-Arenas
Paris A. Mier-Maldonado
Juan Carlos García-Ramos
Nina Bogdanchikova
Alexey Pestryakov
Yanis Toledano-Magaña
author_facet Omar Ulises Cruz-Ramírez
Lucía Margarita Valenzuela-Salas
Alberto Blanco-Salazar
José Antonio Rodríguez-Arenas
Paris A. Mier-Maldonado
Juan Carlos García-Ramos
Nina Bogdanchikova
Alexey Pestryakov
Yanis Toledano-Magaña
author_sort Omar Ulises Cruz-Ramírez
collection DOAJ
description 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% <i>w</i>/<i>w</i>, PVP: 19.6–24.5% and H<sub>2</sub>O: 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.
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spelling doaj.art-b01c4a5f749c4e25b9b5ae83e9635cae2023-11-22T04:40:30ZengMDPI AGPharmaceutics1999-49232021-07-01137100010.3390/pharmaceutics13071000Antitumor Activity against Human Colorectal Adenocarcinoma of Silver Nanoparticles: Influence of [Ag]/[PVP] RatioOmar Ulises Cruz-Ramírez0Lucía Margarita Valenzuela-Salas1Alberto Blanco-Salazar2José Antonio Rodríguez-Arenas3Paris A. Mier-Maldonado4Juan Carlos García-Ramos5Nina Bogdanchikova6Alexey Pestryakov7Yanis Toledano-Magaña8Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Ensenada 22860, MexicoFacultad de Ciencias de la Salud Unidad Valle de las Palmas, Universidad Autónoma de Baja California, Tijuana 22260, MexicoPrograma de Maestría y Doctorado en Ciencias e Ingeniería, Facultad de Ciencias, Universidad Autónoma de Baja California, Ensenada 22860, MexicoPrograma de Maestría y Doctorado en Ciencias e Ingeniería, Facultad de Ciencias, Universidad Autónoma de Baja California, Ensenada 22860, MexicoFacultad de Ciencias de la Salud Unidad Valle de las Palmas, Universidad Autónoma de Baja California, Tijuana 22260, MexicoEscuela de Ciencias de la Salud Unidad Valle Dorado, Universidad Autónoma de Baja California, Ensenada 22890, MexicoCentro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Ensenada 22860, MexicoResearch School of Chemistry & Applied Biomedical Sciences, National Research Tomsk Polytechnic University, 634050 Tomsk, RussiaEscuela de Ciencias de la Salud Unidad Valle Dorado, Universidad Autónoma de Baja California, Ensenada 22890, MexicoSilver 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% <i>w</i>/<i>w</i>, PVP: 19.6–24.5% and H<sub>2</sub>O: 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.https://www.mdpi.com/1999-4923/13/7/1000AgNPsantitumor activitycolon cancerHCT-15cytotoxic selectivity[metal]/[coating agent] ratio
spellingShingle Omar Ulises Cruz-Ramírez
Lucía Margarita Valenzuela-Salas
Alberto Blanco-Salazar
José Antonio Rodríguez-Arenas
Paris A. Mier-Maldonado
Juan Carlos García-Ramos
Nina Bogdanchikova
Alexey Pestryakov
Yanis Toledano-Magaña
Antitumor Activity against Human Colorectal Adenocarcinoma of Silver Nanoparticles: Influence of [Ag]/[PVP] Ratio
Pharmaceutics
AgNPs
antitumor activity
colon cancer
HCT-15
cytotoxic selectivity
[metal]/[coating agent] ratio
title Antitumor Activity against Human Colorectal Adenocarcinoma of Silver Nanoparticles: Influence of [Ag]/[PVP] Ratio
title_full Antitumor Activity against Human Colorectal Adenocarcinoma of Silver Nanoparticles: Influence of [Ag]/[PVP] Ratio
title_fullStr Antitumor Activity against Human Colorectal Adenocarcinoma of Silver Nanoparticles: Influence of [Ag]/[PVP] Ratio
title_full_unstemmed Antitumor Activity against Human Colorectal Adenocarcinoma of Silver Nanoparticles: Influence of [Ag]/[PVP] Ratio
title_short Antitumor Activity against Human Colorectal Adenocarcinoma of Silver Nanoparticles: Influence of [Ag]/[PVP] Ratio
title_sort antitumor activity against human colorectal adenocarcinoma of silver nanoparticles influence of ag pvp ratio
topic AgNPs
antitumor activity
colon cancer
HCT-15
cytotoxic selectivity
[metal]/[coating agent] ratio
url https://www.mdpi.com/1999-4923/13/7/1000
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