Document Detail


Cell-specific radiosensitization by gold nanoparticles at megavoltage radiation energies.
MedLine Citation:
PMID:  21095075     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Gold nanoparticles (GNPs) have been shown to cause sensitization with kilovoltage (kV) radiation. Differences in the absorption coefficient between gold and soft tissue, as a function of photon energy, predict that maximum enhancement should occur in the kilovoltage (kV) range, with almost no enhancement at megavoltage (MV) energies. Recent studies have shown that GNPs are not biologically inert, causing oxidative stress and even cell death, suggesting a possible biological mechanism for sensitization. The purpose of this study was to assess GNP radiosensitization at clinically relevant MV X-ray energies.
METHODS AND MATERIALS: Cellular uptake, intracellular localization, and cytotoxicity of GNPs were assessed in normal L132, prostate cancer DU145, and breast cancer MDA-MB-231 cells. Radiosensitization was measured by clonogenic survival at kV and MV photon energies and MV electron energies. Intracellular DNA double-strand break (DSB) induction and DNA repair were determined and GNP chemosensitization was assessed using the radiomimetic agent bleomycin.
RESULTS: GNP uptake occurred in all cell lines and was greatest in MDA-MB-231 cells with nanoparticles accumulating in cytoplasmic lysosomes. In MDA-MB-231 cells, radiation sensitizer enhancement ratios (SERs) of 1.41, 1.29, and 1.16 were achieved using 160 kVp, 6 MV, and 15 MV X-ray energies, respectively. No significant effect was observed in L132 or DU145 cells at kV or MV energies (SER 0.97-1.08). GNP exposure did not increase radiation-induced DSB formation or inhibit DNA repair; however, GNP chemosensitization was observed in MDA-MB-231 cells treated with bleomycin (SER 1.38).
CONCLUSIONS: We have demonstrated radiosensitization in MDA-MB-231 cells at MV X-ray energies. The sensitization was cell-specific with comparable effects at kV and MV energies, no increase in DSB formation, and GNP chemopotentiation with bleomycin, suggesting a possible biological mechanism of radiosensitization.
Authors:
Suneil Jain; Jonathan A Coulter; Alan R Hounsell; Karl T Butterworth; Stephen J McMahon; Wendy B Hyland; Mark F Muir; Glenn R Dickson; Kevin M Prise; Fred J Currell; Joe M O'Sullivan; David G Hirst
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-20
Journal Detail:
Title:  International journal of radiation oncology, biology, physics     Volume:  79     ISSN:  1879-355X     ISO Abbreviation:  Int. J. Radiat. Oncol. Biol. Phys.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-03     Completed Date:  2011-02-01     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  7603616     Medline TA:  Int J Radiat Oncol Biol Phys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  531-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Antibiotics, Antineoplastic / pharmacology
Bleomycin / pharmacology
Breast Neoplasms / drug therapy,  genetics,  metabolism,  radiotherapy
Cell Cycle / radiation effects
Cell Line, Tumor
DNA Breaks, Double-Stranded
DNA Repair / radiation effects
DNA, Neoplasm / radiation effects
Female
Gold / pharmacokinetics,  therapeutic use*
Humans
Lung / metabolism,  radiation effects
Lysosomes / metabolism,  ultrastructure
Male
Metal Nanoparticles / therapeutic use*
Microscopy, Electron, Transmission
Organ Specificity
Prostatic Neoplasms / genetics,  metabolism,  radiotherapy
Radiation Dosage
Radiation Tolerance / drug effects,  radiation effects*
Radiotherapy, High-Energy / methods*
Tumor Stem Cell Assay / methods
Grant Support
ID/Acronym/Agency:
A7047//Cancer Research UK; C1278/A990//Cancer Research UK; C1513/A7047//Cancer Research UK; G0502183//Medical Research Council
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/DNA, Neoplasm; 11056-06-7/Bleomycin; 7440-57-5/Gold
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