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Biological Effect Evaluation of Glutathione-Responsive Cyclodextrin-Based Nanosponges: 2D and 3D Studies
This study aims to evaluate the bioeffects of glutathione-responsive β-cyclodextrin-based nanosponges (GSH-NSs) on two- (2D) and three-dimensional (3D) cell cultures. The bioeffects of two types of GSH-NS formulations, with low (GSH-NS B) and high (GSH-NS D) disulfide-bond content, were evaluated on...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355809/ https://www.ncbi.nlm.nih.gov/pubmed/32560204 http://dx.doi.org/10.3390/molecules25122775 |
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author | Argenziano, Monica Foglietta, Federica Canaparo, Roberto Spagnolo, Rita Della Pepa, Carlo Caldera, Fabrizio Trotta, Francesco Serpe, Loredana Cavalli, Roberta |
author_facet | Argenziano, Monica Foglietta, Federica Canaparo, Roberto Spagnolo, Rita Della Pepa, Carlo Caldera, Fabrizio Trotta, Francesco Serpe, Loredana Cavalli, Roberta |
author_sort | Argenziano, Monica |
collection | PubMed |
description | This study aims to evaluate the bioeffects of glutathione-responsive β-cyclodextrin-based nanosponges (GSH-NSs) on two- (2D) and three-dimensional (3D) cell cultures. The bioeffects of two types of GSH-NS formulations, with low (GSH-NS B) and high (GSH-NS D) disulfide-bond content, were evaluated on 2D colorectal (HCT116 and HT-29) and prostatic (DU-145 and PC3) cancer cell cultures. In particular, the cellular uptake of GSH-NS was evaluated, as their effects on cell growth, mitochondrial activity, membrane integrity, cell cycle distribution, mRNA expression, and reactive oxygen species production. The effect of GSH-NSs on cell growth was also evaluated on multicellular spheroids (MCS) and a comparison of the GSH-NS cell growth inhibitory activity, in terms of inhibition concentration (IC)(50) values, was performed between 2D and 3D cell cultures. A significant decrease in 2D cell growth was observed at high GSH-NS concentrations, with the formulation with a low disulfide-bond content, GSH-NS B, being more cytotoxic than the formulation with a high disulfide-bond content, GSH-NS D. The cell growth decrease induced by GSH-NS was owing to G(1) cell cycle arrest. Moreover, a significant down-regulation of mRNA expression of the cyclin genes CDK1, CDK2, and CDK4 and up-regulation of mRNA expression of the cyclin inhibitor genes CDKN1A and CDKN2A were observed. On the other hand, a significant decrease in MCS growth was also observed at high GSH-NS concentrations, but not influenced by the nanosponge disulfide-bond content, with the MCS IC(50) values being significantly higher than those obtained on 2D cell cultures. GSH-NSs are suitable nanocarries as they provoke limited cellular effects, as cell cycle arrest only occurred at concentrations significantly higher than those used for drug delivery. |
format | Online Article Text |
id | pubmed-7355809 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73558092020-07-23 Biological Effect Evaluation of Glutathione-Responsive Cyclodextrin-Based Nanosponges: 2D and 3D Studies Argenziano, Monica Foglietta, Federica Canaparo, Roberto Spagnolo, Rita Della Pepa, Carlo Caldera, Fabrizio Trotta, Francesco Serpe, Loredana Cavalli, Roberta Molecules Article This study aims to evaluate the bioeffects of glutathione-responsive β-cyclodextrin-based nanosponges (GSH-NSs) on two- (2D) and three-dimensional (3D) cell cultures. The bioeffects of two types of GSH-NS formulations, with low (GSH-NS B) and high (GSH-NS D) disulfide-bond content, were evaluated on 2D colorectal (HCT116 and HT-29) and prostatic (DU-145 and PC3) cancer cell cultures. In particular, the cellular uptake of GSH-NS was evaluated, as their effects on cell growth, mitochondrial activity, membrane integrity, cell cycle distribution, mRNA expression, and reactive oxygen species production. The effect of GSH-NSs on cell growth was also evaluated on multicellular spheroids (MCS) and a comparison of the GSH-NS cell growth inhibitory activity, in terms of inhibition concentration (IC)(50) values, was performed between 2D and 3D cell cultures. A significant decrease in 2D cell growth was observed at high GSH-NS concentrations, with the formulation with a low disulfide-bond content, GSH-NS B, being more cytotoxic than the formulation with a high disulfide-bond content, GSH-NS D. The cell growth decrease induced by GSH-NS was owing to G(1) cell cycle arrest. Moreover, a significant down-regulation of mRNA expression of the cyclin genes CDK1, CDK2, and CDK4 and up-regulation of mRNA expression of the cyclin inhibitor genes CDKN1A and CDKN2A were observed. On the other hand, a significant decrease in MCS growth was also observed at high GSH-NS concentrations, but not influenced by the nanosponge disulfide-bond content, with the MCS IC(50) values being significantly higher than those obtained on 2D cell cultures. GSH-NSs are suitable nanocarries as they provoke limited cellular effects, as cell cycle arrest only occurred at concentrations significantly higher than those used for drug delivery. MDPI 2020-06-16 /pmc/articles/PMC7355809/ /pubmed/32560204 http://dx.doi.org/10.3390/molecules25122775 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Argenziano, Monica Foglietta, Federica Canaparo, Roberto Spagnolo, Rita Della Pepa, Carlo Caldera, Fabrizio Trotta, Francesco Serpe, Loredana Cavalli, Roberta Biological Effect Evaluation of Glutathione-Responsive Cyclodextrin-Based Nanosponges: 2D and 3D Studies |
title | Biological Effect Evaluation of Glutathione-Responsive Cyclodextrin-Based Nanosponges: 2D and 3D Studies |
title_full | Biological Effect Evaluation of Glutathione-Responsive Cyclodextrin-Based Nanosponges: 2D and 3D Studies |
title_fullStr | Biological Effect Evaluation of Glutathione-Responsive Cyclodextrin-Based Nanosponges: 2D and 3D Studies |
title_full_unstemmed | Biological Effect Evaluation of Glutathione-Responsive Cyclodextrin-Based Nanosponges: 2D and 3D Studies |
title_short | Biological Effect Evaluation of Glutathione-Responsive Cyclodextrin-Based Nanosponges: 2D and 3D Studies |
title_sort | biological effect evaluation of glutathione-responsive cyclodextrin-based nanosponges: 2d and 3d studies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355809/ https://www.ncbi.nlm.nih.gov/pubmed/32560204 http://dx.doi.org/10.3390/molecules25122775 |
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