Use of DNA-generated gold nanoparticles to radiosensitize and eradicate radioresistant glioma stem cells

• Published in: Nanotechnology Vol. 30; no. 5; pp. 055101 - 55111
• Main Authors: Kunoh, Tatsuki, Shimura, Tsutomu, Kasai, Tomonari, Matsumoto, Syuji, Mahmud, Hafizah, Khayrani, Apriliana Cahya, Seno, Masaharu, Kunoh, Hitoshi, Takada, Jun
• Format: Journal Article
• Language: English
• Published: England IOP Publishing 01.02.2019
• Subjects: Annexins - metabolism; Apoptosis - drug effects; Cell Line, Tumor; DNA - administration & dosage; DNA Damage - drug effects; DNA-generated AuNPs; Fluorescent Dyes - administration & dosage; Glioblastoma - metabolism; Glioblastoma - radiotherapy; Glioma - metabolism; Glioma - radiotherapy; glioma stem cells; Gold - administration & dosage; Histones - metabolism; Humans; Metal Nanoparticles - administration & dosage; Mitosis - drug effects; mitotic catastrophe; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Radiation Tolerance - drug effects; radiosensitizer; Reactive Oxygen Species - metabolism; x-ray-irradiation
• ISSN: 0957-4484; 1361-6528
• DOI: 10.1088/1361-6528/aaedd5

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.