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

• Published in: International journal of nanomedicine Vol. 8; no. 1; pp. 2239 - 2246
• Main Authors: Guo, Shuyuan, Sun, Xin, Cheng, Jiali, Xu, Haobo, Dan, Juhua, Shen, Jing, Zhou, Qi, Zhang, Yun, Meng, Lingli, Cao, Wenwu, Tian, Ye
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2013; Taylor & Francis Ltd; Dove Press; Dove Medical Press
• Subjects: Active oxygen; Apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Atherosclerosis; atherosclerotic plaque; Care and treatment; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - radiation effects; cytoskeleton; Cytoskeleton - drug effects; Cytoskeleton - radiation effects; Humans; macrophage; Macrophages; Macrophages - drug effects; Macrophages - radiation effects; Necrosis; Original Research; Physiological aspects; protoporphyrin IX; Protoporphyrins - chemistry; Protoporphyrins - metabolism; Protoporphyrins - pharmacology; Protoporphyrins - radiation effects; singlet oxygen; Singlet Oxygen - metabolism; Sonication - methods; sonodynamic therapy; Statistics, Nonparametric; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Helper-Inducer - radiation effects; Ultrasonic imaging; United States; China; macrophage; sonodynamic therapy; protoporphyrin IX; singlet oxygen; cytoskeleton; atherosclerotic plaque
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S43717

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. 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. 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.