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2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy
An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation, tumor progression and metastasis. This makes iron metabolism an attractive therapeutic target. Unfortunately, current iron-based therapeutic strategies often lack effectiveness and...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
KeAi Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892152/ https://www.ncbi.nlm.nih.gov/pubmed/35310350 http://dx.doi.org/10.1016/j.bioactmat.2021.12.011 |
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author | Xu, Yunjie Wang, Yingwei An, Jusung Sedgwick, Adam C. Li, Mingle Xie, Jianlei Hu, Weibin Kang, Jianlong Sen, Sajal Steinbrueck, Axel Zhang, Bin Qiao, Lijun Wageh, Swelm Arambula, Jonathan F. Liu, Liping Zhang, Han Sessler, Jonathan L. Kim, Jong Seung |
author_facet | Xu, Yunjie Wang, Yingwei An, Jusung Sedgwick, Adam C. Li, Mingle Xie, Jianlei Hu, Weibin Kang, Jianlong Sen, Sajal Steinbrueck, Axel Zhang, Bin Qiao, Lijun Wageh, Swelm Arambula, Jonathan F. Liu, Liping Zhang, Han Sessler, Jonathan L. Kim, Jong Seung |
author_sort | Xu, Yunjie |
collection | PubMed |
description | An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation, tumor progression and metastasis. This makes iron metabolism an attractive therapeutic target. Unfortunately, current iron-based therapeutic strategies often lack effectiveness and can elicit off-target toxicities. We report here a dual-therapeutic prodrug, DOXjade, that allows for iron chelation chemo-photothermal cancer therapy. This prodrug takes advantage of the clinically approved iron chelator deferasirox (ExJade®) and the topoisomerase 2 inhibitor, doxorubicin (DOX). Loading DOXjade onto ultrathin 2D Ti(3)C(2) MXene nanosheets produces a construct, Ti(3)C(2)-PVP@DOXjade, that allows the iron chelation and chemotherapeutic functions of DOXjade to be photo-activated at the tumor sites, while potentiating a robust photothermal effect with photothermal conversion efficiencies of up to 40%. Antitumor mechanistic investigations reveal that upon activation, Ti(3)C(2)-PVP@DOXjade serves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor (TfR). A tumor pH-responsive iron chelation/photothermal/chemotherapy antitumor effect was achieved both in vitro and in vivo. The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy. |
format | Online Article Text |
id | pubmed-8892152 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | KeAi Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-88921522022-03-17 2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy Xu, Yunjie Wang, Yingwei An, Jusung Sedgwick, Adam C. Li, Mingle Xie, Jianlei Hu, Weibin Kang, Jianlong Sen, Sajal Steinbrueck, Axel Zhang, Bin Qiao, Lijun Wageh, Swelm Arambula, Jonathan F. Liu, Liping Zhang, Han Sessler, Jonathan L. Kim, Jong Seung Bioact Mater Article An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation, tumor progression and metastasis. This makes iron metabolism an attractive therapeutic target. Unfortunately, current iron-based therapeutic strategies often lack effectiveness and can elicit off-target toxicities. We report here a dual-therapeutic prodrug, DOXjade, that allows for iron chelation chemo-photothermal cancer therapy. This prodrug takes advantage of the clinically approved iron chelator deferasirox (ExJade®) and the topoisomerase 2 inhibitor, doxorubicin (DOX). Loading DOXjade onto ultrathin 2D Ti(3)C(2) MXene nanosheets produces a construct, Ti(3)C(2)-PVP@DOXjade, that allows the iron chelation and chemotherapeutic functions of DOXjade to be photo-activated at the tumor sites, while potentiating a robust photothermal effect with photothermal conversion efficiencies of up to 40%. Antitumor mechanistic investigations reveal that upon activation, Ti(3)C(2)-PVP@DOXjade serves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor (TfR). A tumor pH-responsive iron chelation/photothermal/chemotherapy antitumor effect was achieved both in vitro and in vivo. The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy. KeAi Publishing 2021-12-18 /pmc/articles/PMC8892152/ /pubmed/35310350 http://dx.doi.org/10.1016/j.bioactmat.2021.12.011 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Xu, Yunjie Wang, Yingwei An, Jusung Sedgwick, Adam C. Li, Mingle Xie, Jianlei Hu, Weibin Kang, Jianlong Sen, Sajal Steinbrueck, Axel Zhang, Bin Qiao, Lijun Wageh, Swelm Arambula, Jonathan F. Liu, Liping Zhang, Han Sessler, Jonathan L. Kim, Jong Seung 2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy |
title | 2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy |
title_full | 2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy |
title_fullStr | 2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy |
title_full_unstemmed | 2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy |
title_short | 2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy |
title_sort | 2d-ultrathin mxene/doxjade platform for iron chelation chemo-photothermal therapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892152/ https://www.ncbi.nlm.nih.gov/pubmed/35310350 http://dx.doi.org/10.1016/j.bioactmat.2021.12.011 |
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