Effects of 5-aminolevulinic acid-mediated sonodynamic therapy on macrophages

Jiali Cheng, Xin Sun, Shuyuan Guo, Wei Cao, Haibo Chen, Yinghua Jin, Bo Li, Qiannan Li, Huan Wang, Zhu Wang, Qi Zhou, Peng Wang, Zhiguo Zhang, Wenwu Cao, Ye Tian

Research output: Contribution to journalArticle

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Abstract

Background: Inflammatory cells exhibit an elevated level of protoporphyrin IX (PpIX) after the administration of 5-aminolevulinic acid (ALA). Here, we investigate the sonodynamic effects of ALA-derived PpIX (ALA-PpIX) on macrophages, which are the pivotal inflammatory cells in atherosclerosis. Methods and results: Cultured THP-1 macrophages were incubated with ALA. Fluorescence microscope and fluorescence spectrometer detection showed that intracellular PpIX increased with the concentration of ALA in the incubation solution in a time dependent manner; the highest level of intracellular PpIX was observed after 3-hour incubation. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays demonstrated that lower concentrations (less than 2 mM) of ALA have no influence on cell viability (more than 90% of cells survived), but sonodynamic therapy (SDT) with a low concentration of ALA significantly decreased the survival rate of cells, and the effect was increased with both ALA concentration and ultrasound exposure time. Cell apoptosis and necrosis induced by ALA-mediated SDT (ALA-SDT) were measured using Hoechst 33258 and propidium iodide assay. ALA-SDT induced both cell apoptosis and necrosis, and the maximum apoptosis/necrosis ratio was observed at 6 hours after SDT with 1 mM of ALA and 5 minutes of ultrasound exposure. Flow cytometry analysis showed that ALA-SDT significantly increased late stage apoptotic cells (about 10-fold control). Furthermore, ALA-SDT induced reactive oxygen species generation in THP-1 macrophages immediately after the treatment and a conspicuous loss of mitochondrial membrane potential (MMP) at 6 hours compared with that of the control, ALA alone, and ultrasound alone groups. Conclusion: ALA-SDT exhibited synergistic apoptotic effects on THP-1 macrophages, involving excessive intracellular reactive oxygen species generation and MMP loss. Therefore, ALA-SDT is a potential treatment for atherosclerosis.

Original languageEnglish (US)
Pages (from-to)669-676
Number of pages8
JournalInternational Journal of Nanomedicine
Volume8
DOIs
StatePublished - Feb 13 2013

Fingerprint

Aminolevulinic Acid
Macrophages
Acids
Therapeutics
Cell death
Necrosis
Mitochondrial Membrane Potential
Ultrasonics
Apoptosis
Assays
Reactive Oxygen Species
Atherosclerosis
Fluorescence
Cells
Membranes
Bisbenzimidazole
Oxygen
Flow cytometry
Propidium

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

Cite this

Cheng, Jiali ; Sun, Xin ; Guo, Shuyuan ; Cao, Wei ; Chen, Haibo ; Jin, Yinghua ; Li, Bo ; Li, Qiannan ; Wang, Huan ; Wang, Zhu ; Zhou, Qi ; Wang, Peng ; Zhang, Zhiguo ; Cao, Wenwu ; Tian, Ye. / Effects of 5-aminolevulinic acid-mediated sonodynamic therapy on macrophages. In: International Journal of Nanomedicine. 2013 ; Vol. 8. pp. 669-676.
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title = "Effects of 5-aminolevulinic acid-mediated sonodynamic therapy on macrophages",
abstract = "Background: Inflammatory cells exhibit an elevated level of protoporphyrin IX (PpIX) after the administration of 5-aminolevulinic acid (ALA). Here, we investigate the sonodynamic effects of ALA-derived PpIX (ALA-PpIX) on macrophages, which are the pivotal inflammatory cells in atherosclerosis. Methods and results: Cultured THP-1 macrophages were incubated with ALA. Fluorescence microscope and fluorescence spectrometer detection showed that intracellular PpIX increased with the concentration of ALA in the incubation solution in a time dependent manner; the highest level of intracellular PpIX was observed after 3-hour incubation. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays demonstrated that lower concentrations (less than 2 mM) of ALA have no influence on cell viability (more than 90{\%} of cells survived), but sonodynamic therapy (SDT) with a low concentration of ALA significantly decreased the survival rate of cells, and the effect was increased with both ALA concentration and ultrasound exposure time. Cell apoptosis and necrosis induced by ALA-mediated SDT (ALA-SDT) were measured using Hoechst 33258 and propidium iodide assay. ALA-SDT induced both cell apoptosis and necrosis, and the maximum apoptosis/necrosis ratio was observed at 6 hours after SDT with 1 mM of ALA and 5 minutes of ultrasound exposure. Flow cytometry analysis showed that ALA-SDT significantly increased late stage apoptotic cells (about 10-fold control). Furthermore, ALA-SDT induced reactive oxygen species generation in THP-1 macrophages immediately after the treatment and a conspicuous loss of mitochondrial membrane potential (MMP) at 6 hours compared with that of the control, ALA alone, and ultrasound alone groups. Conclusion: ALA-SDT exhibited synergistic apoptotic effects on THP-1 macrophages, involving excessive intracellular reactive oxygen species generation and MMP loss. Therefore, ALA-SDT is a potential treatment for atherosclerosis.",
author = "Jiali Cheng and Xin Sun and Shuyuan Guo and Wei Cao and Haibo Chen and Yinghua Jin and Bo Li and Qiannan Li and Huan Wang and Zhu Wang and Qi Zhou and Peng Wang and Zhiguo Zhang and Wenwu Cao and Ye Tian",
year = "2013",
month = "2",
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Cheng, J, Sun, X, Guo, S, Cao, W, Chen, H, Jin, Y, Li, B, Li, Q, Wang, H, Wang, Z, Zhou, Q, Wang, P, Zhang, Z, Cao, W & Tian, Y 2013, 'Effects of 5-aminolevulinic acid-mediated sonodynamic therapy on macrophages', International Journal of Nanomedicine, vol. 8, pp. 669-676. https://doi.org/10.2147/IJN.S39844

Effects of 5-aminolevulinic acid-mediated sonodynamic therapy on macrophages. / Cheng, Jiali; Sun, Xin; Guo, Shuyuan; Cao, Wei; Chen, Haibo; Jin, Yinghua; Li, Bo; Li, Qiannan; Wang, Huan; Wang, Zhu; Zhou, Qi; Wang, Peng; Zhang, Zhiguo; Cao, Wenwu; Tian, Ye.

In: International Journal of Nanomedicine, Vol. 8, 13.02.2013, p. 669-676.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of 5-aminolevulinic acid-mediated sonodynamic therapy on macrophages

AU - Cheng, Jiali

AU - Sun, Xin

AU - Guo, Shuyuan

AU - Cao, Wei

AU - Chen, Haibo

AU - Jin, Yinghua

AU - Li, Bo

AU - Li, Qiannan

AU - Wang, Huan

AU - Wang, Zhu

AU - Zhou, Qi

AU - Wang, Peng

AU - Zhang, Zhiguo

AU - Cao, Wenwu

AU - Tian, Ye

PY - 2013/2/13

Y1 - 2013/2/13

N2 - Background: Inflammatory cells exhibit an elevated level of protoporphyrin IX (PpIX) after the administration of 5-aminolevulinic acid (ALA). Here, we investigate the sonodynamic effects of ALA-derived PpIX (ALA-PpIX) on macrophages, which are the pivotal inflammatory cells in atherosclerosis. Methods and results: Cultured THP-1 macrophages were incubated with ALA. Fluorescence microscope and fluorescence spectrometer detection showed that intracellular PpIX increased with the concentration of ALA in the incubation solution in a time dependent manner; the highest level of intracellular PpIX was observed after 3-hour incubation. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays demonstrated that lower concentrations (less than 2 mM) of ALA have no influence on cell viability (more than 90% of cells survived), but sonodynamic therapy (SDT) with a low concentration of ALA significantly decreased the survival rate of cells, and the effect was increased with both ALA concentration and ultrasound exposure time. Cell apoptosis and necrosis induced by ALA-mediated SDT (ALA-SDT) were measured using Hoechst 33258 and propidium iodide assay. ALA-SDT induced both cell apoptosis and necrosis, and the maximum apoptosis/necrosis ratio was observed at 6 hours after SDT with 1 mM of ALA and 5 minutes of ultrasound exposure. Flow cytometry analysis showed that ALA-SDT significantly increased late stage apoptotic cells (about 10-fold control). Furthermore, ALA-SDT induced reactive oxygen species generation in THP-1 macrophages immediately after the treatment and a conspicuous loss of mitochondrial membrane potential (MMP) at 6 hours compared with that of the control, ALA alone, and ultrasound alone groups. Conclusion: ALA-SDT exhibited synergistic apoptotic effects on THP-1 macrophages, involving excessive intracellular reactive oxygen species generation and MMP loss. Therefore, ALA-SDT is a potential treatment for atherosclerosis.

AB - Background: Inflammatory cells exhibit an elevated level of protoporphyrin IX (PpIX) after the administration of 5-aminolevulinic acid (ALA). Here, we investigate the sonodynamic effects of ALA-derived PpIX (ALA-PpIX) on macrophages, which are the pivotal inflammatory cells in atherosclerosis. Methods and results: Cultured THP-1 macrophages were incubated with ALA. Fluorescence microscope and fluorescence spectrometer detection showed that intracellular PpIX increased with the concentration of ALA in the incubation solution in a time dependent manner; the highest level of intracellular PpIX was observed after 3-hour incubation. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays demonstrated that lower concentrations (less than 2 mM) of ALA have no influence on cell viability (more than 90% of cells survived), but sonodynamic therapy (SDT) with a low concentration of ALA significantly decreased the survival rate of cells, and the effect was increased with both ALA concentration and ultrasound exposure time. Cell apoptosis and necrosis induced by ALA-mediated SDT (ALA-SDT) were measured using Hoechst 33258 and propidium iodide assay. ALA-SDT induced both cell apoptosis and necrosis, and the maximum apoptosis/necrosis ratio was observed at 6 hours after SDT with 1 mM of ALA and 5 minutes of ultrasound exposure. Flow cytometry analysis showed that ALA-SDT significantly increased late stage apoptotic cells (about 10-fold control). Furthermore, ALA-SDT induced reactive oxygen species generation in THP-1 macrophages immediately after the treatment and a conspicuous loss of mitochondrial membrane potential (MMP) at 6 hours compared with that of the control, ALA alone, and ultrasound alone groups. Conclusion: ALA-SDT exhibited synergistic apoptotic effects on THP-1 macrophages, involving excessive intracellular reactive oxygen species generation and MMP loss. Therefore, ALA-SDT is a potential treatment for atherosclerosis.

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