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A nanoreactor boosts chemodynamic therapy and ferroptosis for synergistic cancer therapy using molecular amplifier dihydroartemisinin

BACKGROUND: Chemodynamic therapy (CDT) relying on intracellular iron ions and H(2)O(2) is a promising therapeutic strategy due to its tumor selectivity, which is limited by the not enough metal ions or H(2)O(2) supply of tumor microenvironment. Herein, we presented an efficient CDT strategy based on...

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Autores principales: Yang, Xiao-Xin, Xu, Xiang, Wang, Mei-Fang, Xu, Hua-Zhen, Peng, Xing-Chun, Han, Ning, Yu, Ting-Ting, Li, Liu-Gen, Li, Qi-Rui, Chen, Xiao, Wen, Yu, Li, Tong-Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107746/
https://www.ncbi.nlm.nih.gov/pubmed/35568865
http://dx.doi.org/10.1186/s12951-022-01455-0
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author Yang, Xiao-Xin
Xu, Xiang
Wang, Mei-Fang
Xu, Hua-Zhen
Peng, Xing-Chun
Han, Ning
Yu, Ting-Ting
Li, Liu-Gen
Li, Qi-Rui
Chen, Xiao
Wen, Yu
Li, Tong-Fei
author_facet Yang, Xiao-Xin
Xu, Xiang
Wang, Mei-Fang
Xu, Hua-Zhen
Peng, Xing-Chun
Han, Ning
Yu, Ting-Ting
Li, Liu-Gen
Li, Qi-Rui
Chen, Xiao
Wen, Yu
Li, Tong-Fei
author_sort Yang, Xiao-Xin
collection PubMed
description BACKGROUND: Chemodynamic therapy (CDT) relying on intracellular iron ions and H(2)O(2) is a promising therapeutic strategy due to its tumor selectivity, which is limited by the not enough metal ions or H(2)O(2) supply of tumor microenvironment. Herein, we presented an efficient CDT strategy based on Chinese herbal monomer-dihydroartemisinin (DHA) as a substitute for the H(2)O(2) and recruiter of iron ions to amplify greatly the reactive oxygen species (ROS) generation for synergetic CDT-ferroptosis therapy. RESULTS: The DHA@MIL-101 nanoreactor was prepared and characterized firstly. This nanoreactor degraded under the acid tumor microenvironment, thereby releasing DHA and iron ions. Subsequent experiments demonstrated DHA@MIL-101 significantly increased intracellular iron ions through collapsed nanoreactor and recruitment effect of DHA, further generating ROS thereupon. Meanwhile, ROS production introduced ferroptosis by depleting glutathione (GSH), inactivating glutathione peroxidase 4 (GPX4), leading to lipid peroxide (LPO) accumulation. Furthermore, DHA also acted as an efficient ferroptosis molecular amplifier by direct inhibiting GPX4. The resulting ROS and LPO caused DNA and mitochondria damage to induce apoptosis of malignant cells. Finally, in vivo outcomes evidenced that DHA@MIL-101 nanoreactor exhibited prominent anti-cancer efficacy with minimal systemic toxicity. CONCLUSION: In summary, DHA@MIL-101 nanoreactor boosts CDT and ferroptosis for synergistic cancer therapy by molecular amplifier DHA. This work provides a novel and effective approach for synergistic CDT-ferroptosis with Chinese herbal monomer-DHA and Nanomedicine. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01455-0.
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spelling pubmed-91077462022-05-16 A nanoreactor boosts chemodynamic therapy and ferroptosis for synergistic cancer therapy using molecular amplifier dihydroartemisinin Yang, Xiao-Xin Xu, Xiang Wang, Mei-Fang Xu, Hua-Zhen Peng, Xing-Chun Han, Ning Yu, Ting-Ting Li, Liu-Gen Li, Qi-Rui Chen, Xiao Wen, Yu Li, Tong-Fei J Nanobiotechnology Research BACKGROUND: Chemodynamic therapy (CDT) relying on intracellular iron ions and H(2)O(2) is a promising therapeutic strategy due to its tumor selectivity, which is limited by the not enough metal ions or H(2)O(2) supply of tumor microenvironment. Herein, we presented an efficient CDT strategy based on Chinese herbal monomer-dihydroartemisinin (DHA) as a substitute for the H(2)O(2) and recruiter of iron ions to amplify greatly the reactive oxygen species (ROS) generation for synergetic CDT-ferroptosis therapy. RESULTS: The DHA@MIL-101 nanoreactor was prepared and characterized firstly. This nanoreactor degraded under the acid tumor microenvironment, thereby releasing DHA and iron ions. Subsequent experiments demonstrated DHA@MIL-101 significantly increased intracellular iron ions through collapsed nanoreactor and recruitment effect of DHA, further generating ROS thereupon. Meanwhile, ROS production introduced ferroptosis by depleting glutathione (GSH), inactivating glutathione peroxidase 4 (GPX4), leading to lipid peroxide (LPO) accumulation. Furthermore, DHA also acted as an efficient ferroptosis molecular amplifier by direct inhibiting GPX4. The resulting ROS and LPO caused DNA and mitochondria damage to induce apoptosis of malignant cells. Finally, in vivo outcomes evidenced that DHA@MIL-101 nanoreactor exhibited prominent anti-cancer efficacy with minimal systemic toxicity. CONCLUSION: In summary, DHA@MIL-101 nanoreactor boosts CDT and ferroptosis for synergistic cancer therapy by molecular amplifier DHA. This work provides a novel and effective approach for synergistic CDT-ferroptosis with Chinese herbal monomer-DHA and Nanomedicine. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01455-0. BioMed Central 2022-05-14 /pmc/articles/PMC9107746/ /pubmed/35568865 http://dx.doi.org/10.1186/s12951-022-01455-0 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
Yang, Xiao-Xin
Xu, Xiang
Wang, Mei-Fang
Xu, Hua-Zhen
Peng, Xing-Chun
Han, Ning
Yu, Ting-Ting
Li, Liu-Gen
Li, Qi-Rui
Chen, Xiao
Wen, Yu
Li, Tong-Fei
A nanoreactor boosts chemodynamic therapy and ferroptosis for synergistic cancer therapy using molecular amplifier dihydroartemisinin
title A nanoreactor boosts chemodynamic therapy and ferroptosis for synergistic cancer therapy using molecular amplifier dihydroartemisinin
title_full A nanoreactor boosts chemodynamic therapy and ferroptosis for synergistic cancer therapy using molecular amplifier dihydroartemisinin
title_fullStr A nanoreactor boosts chemodynamic therapy and ferroptosis for synergistic cancer therapy using molecular amplifier dihydroartemisinin
title_full_unstemmed A nanoreactor boosts chemodynamic therapy and ferroptosis for synergistic cancer therapy using molecular amplifier dihydroartemisinin
title_short A nanoreactor boosts chemodynamic therapy and ferroptosis for synergistic cancer therapy using molecular amplifier dihydroartemisinin
title_sort nanoreactor boosts chemodynamic therapy and ferroptosis for synergistic cancer therapy using molecular amplifier dihydroartemisinin
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107746/
https://www.ncbi.nlm.nih.gov/pubmed/35568865
http://dx.doi.org/10.1186/s12951-022-01455-0
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