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Design and Synthesis of a Mitochondria-Targeting Radioprotectant for Promoting Skin Wound Healing Combined with Ionizing Radiation Injury
Wound healing is seriously retarded when combined with ionizing radiation injury, because radiation-induced excessive reactive oxygen species (ROS) profoundly affect cell growth and wound healing. Mitochondria play vital roles not only as cellular energy factories but also as the main source of endo...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229538/ https://www.ncbi.nlm.nih.gov/pubmed/35745640 http://dx.doi.org/10.3390/ph15060721 |
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author | Du, Zaizhi Liu, Han Huang, Xie Li, Yang Wang, Liting Liu, Jing Long, Shuang Li, Rong Xiang, Qiang Luo, Shenglin |
author_facet | Du, Zaizhi Liu, Han Huang, Xie Li, Yang Wang, Liting Liu, Jing Long, Shuang Li, Rong Xiang, Qiang Luo, Shenglin |
author_sort | Du, Zaizhi |
collection | PubMed |
description | Wound healing is seriously retarded when combined with ionizing radiation injury, because radiation-induced excessive reactive oxygen species (ROS) profoundly affect cell growth and wound healing. Mitochondria play vital roles not only as cellular energy factories but also as the main source of endogenous ROS, and in this work a mitochondria-targeting radioprotectant (CY-TMP1) is reported for radiation injury-combined wound repair. It was designed, synthesized and screened out from different conjugates between mitochondria-targeting heptamethine cyanine dyes and a peroxidation inhibitor 2,2,6,6-tetramethylpiperidinyloxy (TEMPO). CY-TMP1 specifically accumulated in mitochondria, efficiently mitigated mitochondrial ROS and total intracellular ROS induced by 6 Gy of X-ray ionizing irradiation, thereby exhibiting a notable radioprotective effect. The mechanism study further demonstrated that CY-TMP1 protected mitochondria from radiation-induced injury, including maintaining mitochondrial membrane potential (MMP) and ATP generation, thereby reducing the ratio of cell apoptotic death. Particularly, an in vivo experiment showed that CY-TMP1 could effectively accelerate wound closure of mice after 6 Gy of whole-body ionizing radiation. Immunohistochemical staining further indicated that CY-TMP1 may improve wound repair through angiogenesis and re-epithelialization. Therefore, mitochondria-targeting ROS scavengers may present a feasible strategy to conquer refractory wound combined with radiation injury. |
format | Online Article Text |
id | pubmed-9229538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92295382022-06-25 Design and Synthesis of a Mitochondria-Targeting Radioprotectant for Promoting Skin Wound Healing Combined with Ionizing Radiation Injury Du, Zaizhi Liu, Han Huang, Xie Li, Yang Wang, Liting Liu, Jing Long, Shuang Li, Rong Xiang, Qiang Luo, Shenglin Pharmaceuticals (Basel) Article Wound healing is seriously retarded when combined with ionizing radiation injury, because radiation-induced excessive reactive oxygen species (ROS) profoundly affect cell growth and wound healing. Mitochondria play vital roles not only as cellular energy factories but also as the main source of endogenous ROS, and in this work a mitochondria-targeting radioprotectant (CY-TMP1) is reported for radiation injury-combined wound repair. It was designed, synthesized and screened out from different conjugates between mitochondria-targeting heptamethine cyanine dyes and a peroxidation inhibitor 2,2,6,6-tetramethylpiperidinyloxy (TEMPO). CY-TMP1 specifically accumulated in mitochondria, efficiently mitigated mitochondrial ROS and total intracellular ROS induced by 6 Gy of X-ray ionizing irradiation, thereby exhibiting a notable radioprotective effect. The mechanism study further demonstrated that CY-TMP1 protected mitochondria from radiation-induced injury, including maintaining mitochondrial membrane potential (MMP) and ATP generation, thereby reducing the ratio of cell apoptotic death. Particularly, an in vivo experiment showed that CY-TMP1 could effectively accelerate wound closure of mice after 6 Gy of whole-body ionizing radiation. Immunohistochemical staining further indicated that CY-TMP1 may improve wound repair through angiogenesis and re-epithelialization. Therefore, mitochondria-targeting ROS scavengers may present a feasible strategy to conquer refractory wound combined with radiation injury. MDPI 2022-06-06 /pmc/articles/PMC9229538/ /pubmed/35745640 http://dx.doi.org/10.3390/ph15060721 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Du, Zaizhi Liu, Han Huang, Xie Li, Yang Wang, Liting Liu, Jing Long, Shuang Li, Rong Xiang, Qiang Luo, Shenglin Design and Synthesis of a Mitochondria-Targeting Radioprotectant for Promoting Skin Wound Healing Combined with Ionizing Radiation Injury |
title | Design and Synthesis of a Mitochondria-Targeting Radioprotectant for Promoting Skin Wound Healing Combined with Ionizing Radiation Injury |
title_full | Design and Synthesis of a Mitochondria-Targeting Radioprotectant for Promoting Skin Wound Healing Combined with Ionizing Radiation Injury |
title_fullStr | Design and Synthesis of a Mitochondria-Targeting Radioprotectant for Promoting Skin Wound Healing Combined with Ionizing Radiation Injury |
title_full_unstemmed | Design and Synthesis of a Mitochondria-Targeting Radioprotectant for Promoting Skin Wound Healing Combined with Ionizing Radiation Injury |
title_short | Design and Synthesis of a Mitochondria-Targeting Radioprotectant for Promoting Skin Wound Healing Combined with Ionizing Radiation Injury |
title_sort | design and synthesis of a mitochondria-targeting radioprotectant for promoting skin wound healing combined with ionizing radiation injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229538/ https://www.ncbi.nlm.nih.gov/pubmed/35745640 http://dx.doi.org/10.3390/ph15060721 |
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