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A multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced chemodynamic therapy

Chemodynamic therapy (CDT) eradicates tumors by intratumoral catalytic chemical reaction and subsequently disrupts redox homeostasis, which shows tumor specific reactive oxygen species (ROS)-mediated therapy. However, insufficient ROS generation and high levels of glutathione (GSH) in cancer cells h...

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Autores principales: Zhong, Wenzhao, Guo, Feng, Chen, Fangman, Law, Man-Kay, Lu, Jun, Shao, Dan, Yu, Hua, Chan, Ging, Chen, Meiwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9689698/
https://www.ncbi.nlm.nih.gov/pubmed/36438812
http://dx.doi.org/10.3389/fphar.2022.1044083
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author Zhong, Wenzhao
Guo, Feng
Chen, Fangman
Law, Man-Kay
Lu, Jun
Shao, Dan
Yu, Hua
Chan, Ging
Chen, Meiwan
author_facet Zhong, Wenzhao
Guo, Feng
Chen, Fangman
Law, Man-Kay
Lu, Jun
Shao, Dan
Yu, Hua
Chan, Ging
Chen, Meiwan
author_sort Zhong, Wenzhao
collection PubMed
description Chemodynamic therapy (CDT) eradicates tumors by intratumoral catalytic chemical reaction and subsequently disrupts redox homeostasis, which shows tumor specific reactive oxygen species (ROS)-mediated therapy. However, insufficient ROS generation and high levels of glutathione (GSH) in cancer cells have limited the therapeutic efficacy of CDT. Herein, we constructed a multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced CDT. Such a sandwich-like nanoamplifier comprised layer-by-layer artesunate (AS) and calcium carbonate coatings on the surface of manganese dioxide (MnO(2)) nanoparticles. The nanoamplifier was disassembled under an acidic environment once accumulated into tumor sites, and subsequently released AS to replenish the intratumoral peroxide pool for ROS amplification. Besides being an AS carrier, MnO(2) exhausted GSH to yield Mn(2+) ions that catalyzed the overexpression of H(2)O(2) in the tumor, further intensifying the oxidative stress and facilitating cancer cell death. Taken together, our findings not only provide a paradigm for fabricating intratumoral catalytic nanomaterials, but also present a new ROS enhancement strategy to improve anti-tumor efficacy. Our multifunctional oxidative stress nanoamplifier might broaden the future of CDT.
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spelling pubmed-96896982022-11-25 A multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced chemodynamic therapy Zhong, Wenzhao Guo, Feng Chen, Fangman Law, Man-Kay Lu, Jun Shao, Dan Yu, Hua Chan, Ging Chen, Meiwan Front Pharmacol Pharmacology Chemodynamic therapy (CDT) eradicates tumors by intratumoral catalytic chemical reaction and subsequently disrupts redox homeostasis, which shows tumor specific reactive oxygen species (ROS)-mediated therapy. However, insufficient ROS generation and high levels of glutathione (GSH) in cancer cells have limited the therapeutic efficacy of CDT. Herein, we constructed a multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced CDT. Such a sandwich-like nanoamplifier comprised layer-by-layer artesunate (AS) and calcium carbonate coatings on the surface of manganese dioxide (MnO(2)) nanoparticles. The nanoamplifier was disassembled under an acidic environment once accumulated into tumor sites, and subsequently released AS to replenish the intratumoral peroxide pool for ROS amplification. Besides being an AS carrier, MnO(2) exhausted GSH to yield Mn(2+) ions that catalyzed the overexpression of H(2)O(2) in the tumor, further intensifying the oxidative stress and facilitating cancer cell death. Taken together, our findings not only provide a paradigm for fabricating intratumoral catalytic nanomaterials, but also present a new ROS enhancement strategy to improve anti-tumor efficacy. Our multifunctional oxidative stress nanoamplifier might broaden the future of CDT. Frontiers Media S.A. 2022-11-10 /pmc/articles/PMC9689698/ /pubmed/36438812 http://dx.doi.org/10.3389/fphar.2022.1044083 Text en Copyright © 2022 Zhong, Guo, Chen, Law, Lu, Shao, Yu, Chan and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhong, Wenzhao
Guo, Feng
Chen, Fangman
Law, Man-Kay
Lu, Jun
Shao, Dan
Yu, Hua
Chan, Ging
Chen, Meiwan
A multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced chemodynamic therapy
title A multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced chemodynamic therapy
title_full A multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced chemodynamic therapy
title_fullStr A multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced chemodynamic therapy
title_full_unstemmed A multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced chemodynamic therapy
title_short A multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced chemodynamic therapy
title_sort multifunctional oxidative stress nanoamplifier with ros amplification and gsh exhaustion for enhanced chemodynamic therapy
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9689698/
https://www.ncbi.nlm.nih.gov/pubmed/36438812
http://dx.doi.org/10.3389/fphar.2022.1044083
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