Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Du, Zaizhi, Liu, Han, Huang, Xie, Li, Yang, Wang, Liting, Liu, Jing, Long, Shuang, Li, Rong, Xiang, Qiang, Luo, Shenglin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784734772564590592
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
work_keys_str_mv AT duzaizhi designandsynthesisofamitochondriatargetingradioprotectantforpromotingskinwoundhealingcombinedwithionizingradiationinjury
AT liuhan designandsynthesisofamitochondriatargetingradioprotectantforpromotingskinwoundhealingcombinedwithionizingradiationinjury
AT huangxie designandsynthesisofamitochondriatargetingradioprotectantforpromotingskinwoundhealingcombinedwithionizingradiationinjury
AT liyang designandsynthesisofamitochondriatargetingradioprotectantforpromotingskinwoundhealingcombinedwithionizingradiationinjury
AT wangliting designandsynthesisofamitochondriatargetingradioprotectantforpromotingskinwoundhealingcombinedwithionizingradiationinjury
AT liujing designandsynthesisofamitochondriatargetingradioprotectantforpromotingskinwoundhealingcombinedwithionizingradiationinjury
AT longshuang designandsynthesisofamitochondriatargetingradioprotectantforpromotingskinwoundhealingcombinedwithionizingradiationinjury
AT lirong designandsynthesisofamitochondriatargetingradioprotectantforpromotingskinwoundhealingcombinedwithionizingradiationinjury
AT xiangqiang designandsynthesisofamitochondriatargetingradioprotectantforpromotingskinwoundhealingcombinedwithionizingradiationinjury
AT luoshenglin designandsynthesisofamitochondriatargetingradioprotectantforpromotingskinwoundhealingcombinedwithionizingradiationinjury