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Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy

Ferroptosis is a new mode of cell death, which can be induced by Fenton reaction-mediated lipid peroxidation. However, the insufficient H(2)O(2) and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ferroptosis. Herein, a self-supplying lipid peroxide nanoreactor was devel...

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Autores principales: Yang, Yinxian, Zuo, Shiyi, Li, Linxiao, Kuang, Xiao, Li, Jinbo, Sun, Bingjun, Wang, Shujun, He, Zhonggui, Sun, Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shenyang Pharmaceutical University 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8737402/
https://www.ncbi.nlm.nih.gov/pubmed/35027953
http://dx.doi.org/10.1016/j.ajps.2021.05.001
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author Yang, Yinxian
Zuo, Shiyi
Li, Linxiao
Kuang, Xiao
Li, Jinbo
Sun, Bingjun
Wang, Shujun
He, Zhonggui
Sun, Jin
author_facet Yang, Yinxian
Zuo, Shiyi
Li, Linxiao
Kuang, Xiao
Li, Jinbo
Sun, Bingjun
Wang, Shujun
He, Zhonggui
Sun, Jin
author_sort Yang, Yinxian
collection PubMed
description Ferroptosis is a new mode of cell death, which can be induced by Fenton reaction-mediated lipid peroxidation. However, the insufficient H(2)O(2) and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ferroptosis. Herein, a self-supplying lipid peroxide nanoreactor was developed to co-delivery of doxorubicin (DOX), iron and unsaturated lipid for efficient ferroptosis. By leveraging the coordination effect between DOX and Fe(3+), trisulfide bond-bridged DOX dimeric prodrug was actively loaded into the core of the unsaturated lipids-rich liposome via iron ion gradient method. First, Fe(3+)could react with the overexpressed GSH in tumor cells, inducing the GSH depletion and Fe(2+)generation. Second, the cleavage of trisulfide bond could also consume GSH, and the released DOX induces the generation of H(2)O(2,) which would react with the generated Fe(2+)in step one to induce efficient Fenton reaction-dependent ferroptosis. Third, the formed Fe(3+)/Fe(2+) couple could directly catalyze peroxidation of unsaturated lipids to boost Fenton reaction-independent ferroptosis. This iron-prodrug liposome nanoreactor precisely programs multimodal ferroptosis by integrating GSH depletion, ROS generation and lipid peroxidation, providing new sights for efficient cancer therapy.
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spelling pubmed-87374022022-01-12 Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy Yang, Yinxian Zuo, Shiyi Li, Linxiao Kuang, Xiao Li, Jinbo Sun, Bingjun Wang, Shujun He, Zhonggui Sun, Jin Asian J Pharm Sci Original Research Paper Ferroptosis is a new mode of cell death, which can be induced by Fenton reaction-mediated lipid peroxidation. However, the insufficient H(2)O(2) and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ferroptosis. Herein, a self-supplying lipid peroxide nanoreactor was developed to co-delivery of doxorubicin (DOX), iron and unsaturated lipid for efficient ferroptosis. By leveraging the coordination effect between DOX and Fe(3+), trisulfide bond-bridged DOX dimeric prodrug was actively loaded into the core of the unsaturated lipids-rich liposome via iron ion gradient method. First, Fe(3+)could react with the overexpressed GSH in tumor cells, inducing the GSH depletion and Fe(2+)generation. Second, the cleavage of trisulfide bond could also consume GSH, and the released DOX induces the generation of H(2)O(2,) which would react with the generated Fe(2+)in step one to induce efficient Fenton reaction-dependent ferroptosis. Third, the formed Fe(3+)/Fe(2+) couple could directly catalyze peroxidation of unsaturated lipids to boost Fenton reaction-independent ferroptosis. This iron-prodrug liposome nanoreactor precisely programs multimodal ferroptosis by integrating GSH depletion, ROS generation and lipid peroxidation, providing new sights for efficient cancer therapy. Shenyang Pharmaceutical University 2021-11 2021-06-06 /pmc/articles/PMC8737402/ /pubmed/35027953 http://dx.doi.org/10.1016/j.ajps.2021.05.001 Text en © 2021 Shenyang Pharmaceutical University. Published by Elsevier B.V. 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 Original Research Paper
Yang, Yinxian
Zuo, Shiyi
Li, Linxiao
Kuang, Xiao
Li, Jinbo
Sun, Bingjun
Wang, Shujun
He, Zhonggui
Sun, Jin
Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy
title Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy
title_full Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy
title_fullStr Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy
title_full_unstemmed Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy
title_short Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy
title_sort iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy
topic Original Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8737402/
https://www.ncbi.nlm.nih.gov/pubmed/35027953
http://dx.doi.org/10.1016/j.ajps.2021.05.001
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