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Increased apoptotic potential and dose-enhancing effect of gold nanoparticles in combination with single-dose clinical electron beams on tumor-bearing mice
Authors:Chang Meng-Ya  Shiau Ai-Li  Chen Yu-Hung  Chang Chih-Jui  Chen Helen H-W  Wu Chao-Liang
Affiliation:Department of Biochemistry and Molecular Biology, National Cheng Kung University Medical College, 1 Dashiue Road, Tainan 701, Taiwan,;Department of Microbiology and Immunology, National Cheng Kung University Hospital 138 Sheng-Li Road, Tainan 701, Taiwan,;Institute of Clinical Medicine, National Cheng Kung University Medical College, Tainan, 701, Taiwan,;Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan, 701, Taiwan
Abstract:High atomic number material, such as gold, may be used in conjunction with radiation to provide dose enhancement in tumors. In the current study, we investigated the dose-enhancing effect and apoptotic potential of gold nanoparticles in combination with single-dose clinical electron beams on B16F10 melanoma tumor-bearing mice. We revealed that the accumulation of gold nanoparticles was detected inside B16F10 culture cells after 18 h of incubation, and moreover, the gold nanoparticles were shown to be colocalized with endoplasmic reticulum and Golgi apparatus in cells. Furthermore, gold nanoparticles radiosensitized melanoma cells in the colony formation assay ( P =  0.02). Using a B16F10 tumor-bearing mouse model, we further demonstrated that gold nanoparticles in conjunction with ionizing radiation significantly retarded tumor growth and prolonged survival compared to the radiation alone controls ( P <  0.05). Importantly, an increase of apoptotic signals was detected inside tumors in the combined treatment group ( P <  0.05). Knowing that radiation-induced apoptosis has been considered a determinant of tumor responses to radiation therapy, and the length of tumor regrowth delay correlated with the extent of apoptosis after single-dose radiotherapy, these results may suggest the clinical potential of gold nanoparticles in improving the outcome of melanoma radiotherapy. ( Cancer Sci 2008; 99: 1479–1484)
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