TY - JOUR
T1 - Use of DNA-generated gold nanoparticles to radiosensitize and eradicate radioresistant glioma stem cells
AU - Kunoh, Tatsuki
AU - Shimura, Tsutomu
AU - Kasai, Tomonari
AU - Matsumoto, Syuji
AU - Mahmud, Hafizah
AU - Khayrani, Apriliana Cahya
AU - Seno, Masaharu
AU - Kunoh, Hitoshi
AU - Takada, Jun
N1 - Funding Information:
We thank Ms Masumi Furutani, Ms Tomomi Tsukano, and Mr Haruo Urata of the Central Research Laboratory at Okayama University Medical School for providing the method for AuNPs sensitization in human cells. We appreciate Dr Megumi Sasatani of Hiroshima University for valuable comments. We also acknowledge Dr Beth E Hazen for reviewing and editing the English in the manuscript. This study was financially supported by JST-CREST (2012–2017) (JT) by JST, and Grant-in-Aid for Challenging Exploratory Research (17K19944) (TS) and for Scientific Research (C) (16K07116) (T Kasai) by JSPS. This work was also supported by the Program of the Network-type Joint Usage/ Research Center for Radiation Disaster Medical Science.
Publisher Copyright:
© 2018 IOP Publishing Ltd.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - The surface reactivity of gold nanoparticles (AuNPs) is receiving attention as a radiosensitizer of cancer cells for radiation therapy and/or as a drug carrier to target cells. This study demonstrates the potential of DNA-AuNPs (prepared by mixing calf thymus DNA with HAuCl4 solution) as a radiosensitizer of human glioma cells that have cancer stem cell (CSC)-like properties, to reduce their survival. CSC-like U251MG-P1 cells and their parental glioblastoma U251MG cells are treated with a prepared DNA-AuNP colloid. The radiosensitivity of the resultant AuNP-associated cells are significantly enhanced. To reveal the mechanism by which survival is reduced, the generation of reactive oxygen species (ROS), apoptosis induction, or DNA damage in the cells is assayed using the fluorescent dye DCFDA, annexin V-FITC/PI, and foci formation of γ-H2AX, respectively. X-ray irradiation with administration of AuNPs overcomes the radioresistance of U251MG-P1 cells. It does not induce ROS generation or apoptosis in the cells but enhances the number of abnormal nuclei with abundant γ-H2AX foci, which is judged as cell death by mitotic catastrophe. The AuNP association with the cells effectively induces mitotic catastrophe in x-ray-irradiated CSC-like cells, implicating that DNA-AuNPs might be a promising tool to develop an efficient radiosensitizer against CSC.
AB - The surface reactivity of gold nanoparticles (AuNPs) is receiving attention as a radiosensitizer of cancer cells for radiation therapy and/or as a drug carrier to target cells. This study demonstrates the potential of DNA-AuNPs (prepared by mixing calf thymus DNA with HAuCl4 solution) as a radiosensitizer of human glioma cells that have cancer stem cell (CSC)-like properties, to reduce their survival. CSC-like U251MG-P1 cells and their parental glioblastoma U251MG cells are treated with a prepared DNA-AuNP colloid. The radiosensitivity of the resultant AuNP-associated cells are significantly enhanced. To reveal the mechanism by which survival is reduced, the generation of reactive oxygen species (ROS), apoptosis induction, or DNA damage in the cells is assayed using the fluorescent dye DCFDA, annexin V-FITC/PI, and foci formation of γ-H2AX, respectively. X-ray irradiation with administration of AuNPs overcomes the radioresistance of U251MG-P1 cells. It does not induce ROS generation or apoptosis in the cells but enhances the number of abnormal nuclei with abundant γ-H2AX foci, which is judged as cell death by mitotic catastrophe. The AuNP association with the cells effectively induces mitotic catastrophe in x-ray-irradiated CSC-like cells, implicating that DNA-AuNPs might be a promising tool to develop an efficient radiosensitizer against CSC.
UR - http://www.scopus.com/inward/record.url?scp=85058463477&partnerID=8YFLogxK
U2 - 10.1088/1361-6528/aaedd5
DO - 10.1088/1361-6528/aaedd5
M3 - Article
C2 - 30499457
AN - SCOPUS:85058463477
SN - 0957-4484
VL - 30
JO - Nanotechnology
JF - Nanotechnology
IS - 5
M1 - 055101
ER -
