Apoptosis of THP-1 macrophages induced by protoporphyrin IX-mediated sonodynamic therapy

Shuyuan Guo,1* Xin Sun,1,2* Jiali Cheng,1 Haobo Xu,1 Juhua Dan,2 Jing Shen,3 Qi Zhou,4 Yun Zhang,1 Lingli Meng,1 Wenwu Cao,4,5 Ye Tian1,2 1Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, People's Republic of China; 2Division...

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Autores principales:	Guo S, Sun X, Cheng J, Xu H, Dan J, Shen J, Zhou Q, Zhang Y, Meng L, Cao W, Tian Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c37733c148414db09a4215e0738ff0ba
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spelling	oai:doaj.org-article:c37733c148414db09a4215e0738ff0ba2021-12-02T02:42:09ZApoptosis of THP-1 macrophages induced by protoporphyrin IX-mediated sonodynamic therapy1176-91141178-2013https://doaj.org/article/c37733c148414db09a4215e0738ff0ba2013-06-01T00:00:00Zhttp://www.dovepress.com/apoptosis-of-thp-1-macrophages-induced-by-protoporphyrin-ix-mediated-s-a13412https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Shuyuan Guo,1* Xin Sun,1,2* Jiali Cheng,1 Haobo Xu,1 Juhua Dan,2 Jing Shen,3 Qi Zhou,4 Yun Zhang,1 Lingli Meng,1 Wenwu Cao,4,5 Ye Tian1,2 1Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, People's Republic of China; 2Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin, People's Republic of China; 3Division of Oncology, the Third Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China; 4Laboratory of Photo- and Sono-theranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, People's Republic of China; 5Department of Mathematics and Materials Research Institute, Pennsylvania State University, University Park, PA, USA *These authors contributed equally to this work Background: Sonodynamic therapy (SDT) was developed as a localized ultrasound-activated cytotoxic therapy for cancer. The ability of SDT to destroy target tissues selectively is especially appealing for atherosclerotic plaque, in which selective accumulation of the sonosensitizer, protoporphyrin IX (PpIX), had been demonstrated. Here we investigate the effects of PpIX-mediated SDT on macrophages, which are the main culprit in progression of atherosclerosis. Methods and results: Cultured THP-1 derived macrophages were incubated with PpIX. Fluorescence microscopy showed that the intracellular PpIX concentration increased with the concentration of PpIX in the incubation medium. MTT assay demonstrated that SDT with PpIX significantly decreased cell viability, and this effect increased with duration of ultrasound exposure and PpIX concentration. PpIX-mediated SDT induced both apoptosis and necrosis, and the maximum apoptosis to necrosis ratio was obtained after SDT with 20 µg/mL PpIX and five minutes of sonication. Production of intracellular singlet oxygen and secondary disruption of the cytoskeleton were also observed after SDT with PpIX. Conclusion: PpIX-mediated SDT had apoptotic effects on THP-1 macrophages via generation of intracellular singlet oxygen and disruption of the cytoskeleton. PpIX-mediated SDT may be a potential treatment to attenuate progression of atherosclerotic plaque. Keywords: sonodynamic therapy, protoporphyrin IX, atherosclerotic plaque, macrophage, singlet oxygen, cytoskeletonGuo SSun XCheng JXu HDan JShen JZhou QZhang YMeng LCao WTian YDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 2239-2246 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Guo S Sun X Cheng J Xu H Dan J Shen J Zhou Q Zhang Y Meng L Cao W Tian Y Apoptosis of THP-1 macrophages induced by protoporphyrin IX-mediated sonodynamic therapy
description	Shuyuan Guo,1* Xin Sun,1,2* Jiali Cheng,1 Haobo Xu,1 Juhua Dan,2 Jing Shen,3 Qi Zhou,4 Yun Zhang,1 Lingli Meng,1 Wenwu Cao,4,5 Ye Tian1,2 1Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, People's Republic of China; 2Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin, People's Republic of China; 3Division of Oncology, the Third Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China; 4Laboratory of Photo- and Sono-theranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, People's Republic of China; 5Department of Mathematics and Materials Research Institute, Pennsylvania State University, University Park, PA, USA *These authors contributed equally to this work Background: Sonodynamic therapy (SDT) was developed as a localized ultrasound-activated cytotoxic therapy for cancer. The ability of SDT to destroy target tissues selectively is especially appealing for atherosclerotic plaque, in which selective accumulation of the sonosensitizer, protoporphyrin IX (PpIX), had been demonstrated. Here we investigate the effects of PpIX-mediated SDT on macrophages, which are the main culprit in progression of atherosclerosis. Methods and results: Cultured THP-1 derived macrophages were incubated with PpIX. Fluorescence microscopy showed that the intracellular PpIX concentration increased with the concentration of PpIX in the incubation medium. MTT assay demonstrated that SDT with PpIX significantly decreased cell viability, and this effect increased with duration of ultrasound exposure and PpIX concentration. PpIX-mediated SDT induced both apoptosis and necrosis, and the maximum apoptosis to necrosis ratio was obtained after SDT with 20 µg/mL PpIX and five minutes of sonication. Production of intracellular singlet oxygen and secondary disruption of the cytoskeleton were also observed after SDT with PpIX. Conclusion: PpIX-mediated SDT had apoptotic effects on THP-1 macrophages via generation of intracellular singlet oxygen and disruption of the cytoskeleton. PpIX-mediated SDT may be a potential treatment to attenuate progression of atherosclerotic plaque. Keywords: sonodynamic therapy, protoporphyrin IX, atherosclerotic plaque, macrophage, singlet oxygen, cytoskeleton
format	article
author	Guo S Sun X Cheng J Xu H Dan J Shen J Zhou Q Zhang Y Meng L Cao W Tian Y
author_facet	Guo S Sun X Cheng J Xu H Dan J Shen J Zhou Q Zhang Y Meng L Cao W Tian Y
author_sort	Guo S
title	Apoptosis of THP-1 macrophages induced by protoporphyrin IX-mediated sonodynamic therapy
title_short	Apoptosis of THP-1 macrophages induced by protoporphyrin IX-mediated sonodynamic therapy
title_full	Apoptosis of THP-1 macrophages induced by protoporphyrin IX-mediated sonodynamic therapy
title_fullStr	Apoptosis of THP-1 macrophages induced by protoporphyrin IX-mediated sonodynamic therapy
title_full_unstemmed	Apoptosis of THP-1 macrophages induced by protoporphyrin IX-mediated sonodynamic therapy
title_sort	apoptosis of thp-1 macrophages induced by protoporphyrin ix-mediated sonodynamic therapy
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/c37733c148414db09a4215e0738ff0ba
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Apoptosis of THP-1 macrophages induced by protoporphyrin IX-mediated sonodynamic therapy

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