Cargando…

Antitumor Effects of Pegylated Zinc Protoporphyrin-Mediated Sonodynamic Therapy in Ovarian Cancer

Sonodynamic therapy (SDT) induces reactive oxygen species (ROS) to kill tumor cells. Heme oxygenase-1 (HO-1), as an important antioxidant enzyme, resists killing by scavenging ROS. Zinc protoporphyrin (ZnPP) not only effectively inhibits HO-1 activity, but also becomes a potential sonosensitizer. Ho...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Jia, Hu, Zheng, Zhu, Jiwei, Lin, Xin, Gao, Xu, Lv, Guixiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10534787/
https://www.ncbi.nlm.nih.gov/pubmed/37765244
http://dx.doi.org/10.3390/pharmaceutics15092275
_version_ 1785112476500623360
author Li, Jia
Hu, Zheng
Zhu, Jiwei
Lin, Xin
Gao, Xu
Lv, Guixiang
author_facet Li, Jia
Hu, Zheng
Zhu, Jiwei
Lin, Xin
Gao, Xu
Lv, Guixiang
author_sort Li, Jia
collection PubMed
description Sonodynamic therapy (SDT) induces reactive oxygen species (ROS) to kill tumor cells. Heme oxygenase-1 (HO-1), as an important antioxidant enzyme, resists killing by scavenging ROS. Zinc protoporphyrin (ZnPP) not only effectively inhibits HO-1 activity, but also becomes a potential sonosensitizer. However, its poor water solubility limits its applications. Herein, we developed an improved water-soluble method. It was proved that pegylated zinc protoporphyrin-mediated SDT (PEG-ZnPP-SDT) could significantly enhance ROS production by destroying the HO-1 antioxidant system in ovarian cancer. Increased ROS could cause mitochondrial membrane potential collapse, release cytochrome c from mitochondria to the cytoplasm, and trigger the mitochondrial–caspase apoptotic pathway. In conclusion, our results demonstrated that PEG-ZnPP-SDT, as a novel sonosensitizer, could improve the antitumor effects by destroying the HO-1 antioxidant system. It provided a new therapeutic strategy for SDT to treat cancers, especially those with higher HO-1 expression.
format Online
Article
Text
id pubmed-10534787
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-105347872023-09-29 Antitumor Effects of Pegylated Zinc Protoporphyrin-Mediated Sonodynamic Therapy in Ovarian Cancer Li, Jia Hu, Zheng Zhu, Jiwei Lin, Xin Gao, Xu Lv, Guixiang Pharmaceutics Article Sonodynamic therapy (SDT) induces reactive oxygen species (ROS) to kill tumor cells. Heme oxygenase-1 (HO-1), as an important antioxidant enzyme, resists killing by scavenging ROS. Zinc protoporphyrin (ZnPP) not only effectively inhibits HO-1 activity, but also becomes a potential sonosensitizer. However, its poor water solubility limits its applications. Herein, we developed an improved water-soluble method. It was proved that pegylated zinc protoporphyrin-mediated SDT (PEG-ZnPP-SDT) could significantly enhance ROS production by destroying the HO-1 antioxidant system in ovarian cancer. Increased ROS could cause mitochondrial membrane potential collapse, release cytochrome c from mitochondria to the cytoplasm, and trigger the mitochondrial–caspase apoptotic pathway. In conclusion, our results demonstrated that PEG-ZnPP-SDT, as a novel sonosensitizer, could improve the antitumor effects by destroying the HO-1 antioxidant system. It provided a new therapeutic strategy for SDT to treat cancers, especially those with higher HO-1 expression. MDPI 2023-09-04 /pmc/articles/PMC10534787/ /pubmed/37765244 http://dx.doi.org/10.3390/pharmaceutics15092275 Text en © 2023 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
Li, Jia
Hu, Zheng
Zhu, Jiwei
Lin, Xin
Gao, Xu
Lv, Guixiang
Antitumor Effects of Pegylated Zinc Protoporphyrin-Mediated Sonodynamic Therapy in Ovarian Cancer
title Antitumor Effects of Pegylated Zinc Protoporphyrin-Mediated Sonodynamic Therapy in Ovarian Cancer
title_full Antitumor Effects of Pegylated Zinc Protoporphyrin-Mediated Sonodynamic Therapy in Ovarian Cancer
title_fullStr Antitumor Effects of Pegylated Zinc Protoporphyrin-Mediated Sonodynamic Therapy in Ovarian Cancer
title_full_unstemmed Antitumor Effects of Pegylated Zinc Protoporphyrin-Mediated Sonodynamic Therapy in Ovarian Cancer
title_short Antitumor Effects of Pegylated Zinc Protoporphyrin-Mediated Sonodynamic Therapy in Ovarian Cancer
title_sort antitumor effects of pegylated zinc protoporphyrin-mediated sonodynamic therapy in ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10534787/
https://www.ncbi.nlm.nih.gov/pubmed/37765244
http://dx.doi.org/10.3390/pharmaceutics15092275
work_keys_str_mv AT lijia antitumoreffectsofpegylatedzincprotoporphyrinmediatedsonodynamictherapyinovariancancer
AT huzheng antitumoreffectsofpegylatedzincprotoporphyrinmediatedsonodynamictherapyinovariancancer
AT zhujiwei antitumoreffectsofpegylatedzincprotoporphyrinmediatedsonodynamictherapyinovariancancer
AT linxin antitumoreffectsofpegylatedzincprotoporphyrinmediatedsonodynamictherapyinovariancancer
AT gaoxu antitumoreffectsofpegylatedzincprotoporphyrinmediatedsonodynamictherapyinovariancancer
AT lvguixiang antitumoreffectsofpegylatedzincprotoporphyrinmediatedsonodynamictherapyinovariancancer