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Engineering 2D Cu-composed metal–organic framework nanosheets for augmented nanocatalytic tumor therapy
The engineered nanoformulation that can be activated by intracellular tumor microenvironment, including acidic pH, overexpressed H(2)O(2), and high concentration of glutathione (GSH), features high efficacy to eradicate tumor cells with the intrinsic specificity and therapeutic biosafety. However, t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8815149/ https://www.ncbi.nlm.nih.gov/pubmed/35120548 http://dx.doi.org/10.1186/s12951-022-01250-x |
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author | Zhuang, Shangwen Xiang, Huijing Chen, Yixin Wang, Lulu Chen, Yu Zhang, Jun |
author_facet | Zhuang, Shangwen Xiang, Huijing Chen, Yixin Wang, Lulu Chen, Yu Zhang, Jun |
author_sort | Zhuang, Shangwen |
collection | PubMed |
description | The engineered nanoformulation that can be activated by intracellular tumor microenvironment, including acidic pH, overexpressed H(2)O(2), and high concentration of glutathione (GSH), features high efficacy to eradicate tumor cells with the intrinsic specificity and therapeutic biosafety. However, the relatively slow reaction rate of traditional Fe(2+)-mediated Fenton reaction induces the low production amount of reactive oxygen species (ROS) and subsequently the limited therapeutic outcome against tumors. Here, we established Cu (II)-based two-dimensional (2D) metal–organic framework (MOF) nanosheets as a distinct chemoreactive nanocatalyst for GSH-triggered and H(2)O(2)-augmented chemodynamic therapy (CDT), depending on the “AND” logic gate, for significant tumor suppression. After internalization by tumor cells, the MOF catalytic nanosheets reacted with local GSH for inducing GSH consumption and reducing the Cu(2+) into Cu(+). Subsequently, abundant hydroxyl radicals (·OH) generation was achieved via Cu(+)-mediated Fenton-like catalytic reaction. The dual effects of ·OH production and GSH depletion thus enhanced ROS production and accumulation in tumor cells, leading to significant cellular apoptosis and tumor inhibition, which was systematically demonstrated in both 4T1 and MDA-MB-231 tumor models. Therefore, GSH and H(2)O(2), serve as an “AND” logic gate to trigger the Cu(+)-mediated Fenton-like reaction and reduce GSH level for augmented CDT with high therapeutic specificity and efficacy, thus inducing cellular apoptosis primarily through ferroptosis at the RNA sequence level. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01250-x. |
format | Online Article Text |
id | pubmed-8815149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-88151492022-02-07 Engineering 2D Cu-composed metal–organic framework nanosheets for augmented nanocatalytic tumor therapy Zhuang, Shangwen Xiang, Huijing Chen, Yixin Wang, Lulu Chen, Yu Zhang, Jun J Nanobiotechnology Research The engineered nanoformulation that can be activated by intracellular tumor microenvironment, including acidic pH, overexpressed H(2)O(2), and high concentration of glutathione (GSH), features high efficacy to eradicate tumor cells with the intrinsic specificity and therapeutic biosafety. However, the relatively slow reaction rate of traditional Fe(2+)-mediated Fenton reaction induces the low production amount of reactive oxygen species (ROS) and subsequently the limited therapeutic outcome against tumors. Here, we established Cu (II)-based two-dimensional (2D) metal–organic framework (MOF) nanosheets as a distinct chemoreactive nanocatalyst for GSH-triggered and H(2)O(2)-augmented chemodynamic therapy (CDT), depending on the “AND” logic gate, for significant tumor suppression. After internalization by tumor cells, the MOF catalytic nanosheets reacted with local GSH for inducing GSH consumption and reducing the Cu(2+) into Cu(+). Subsequently, abundant hydroxyl radicals (·OH) generation was achieved via Cu(+)-mediated Fenton-like catalytic reaction. The dual effects of ·OH production and GSH depletion thus enhanced ROS production and accumulation in tumor cells, leading to significant cellular apoptosis and tumor inhibition, which was systematically demonstrated in both 4T1 and MDA-MB-231 tumor models. Therefore, GSH and H(2)O(2), serve as an “AND” logic gate to trigger the Cu(+)-mediated Fenton-like reaction and reduce GSH level for augmented CDT with high therapeutic specificity and efficacy, thus inducing cellular apoptosis primarily through ferroptosis at the RNA sequence level. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01250-x. BioMed Central 2022-02-04 /pmc/articles/PMC8815149/ /pubmed/35120548 http://dx.doi.org/10.1186/s12951-022-01250-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Zhuang, Shangwen Xiang, Huijing Chen, Yixin Wang, Lulu Chen, Yu Zhang, Jun Engineering 2D Cu-composed metal–organic framework nanosheets for augmented nanocatalytic tumor therapy |
title | Engineering 2D Cu-composed metal–organic framework nanosheets for augmented nanocatalytic tumor therapy |
title_full | Engineering 2D Cu-composed metal–organic framework nanosheets for augmented nanocatalytic tumor therapy |
title_fullStr | Engineering 2D Cu-composed metal–organic framework nanosheets for augmented nanocatalytic tumor therapy |
title_full_unstemmed | Engineering 2D Cu-composed metal–organic framework nanosheets for augmented nanocatalytic tumor therapy |
title_short | Engineering 2D Cu-composed metal–organic framework nanosheets for augmented nanocatalytic tumor therapy |
title_sort | engineering 2d cu-composed metal–organic framework nanosheets for augmented nanocatalytic tumor therapy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8815149/ https://www.ncbi.nlm.nih.gov/pubmed/35120548 http://dx.doi.org/10.1186/s12951-022-01250-x |
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