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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Shenyang Pharmaceutical University
2021
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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. |
format | Online Article Text |
id | pubmed-8737402 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Shenyang Pharmaceutical University |
record_format | MEDLINE/PubMed |
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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