title: The radiosensitization effect of titanate nanotubes as a new tool in radiation therapy for glioblastoma: a proof-of-concept.
abstract: OBJECTIVE
  One of the new challenges to improve radiotherapy is to increase the ionizing effect by using nanoparticles. The interest of titanate nanotubes (TiONts) associated with radiotherapy was evaluated in two human glioblastoma cell lines (SNB-19 and U87MG).
  
  
  METHODS
  Titanate nanotubes were synthetized by the hydrothermal treatment of titanium dioxide powder in a strongly basic NaOH solution. The cytotoxicity of TiONts was evaluated on SNB-19 and U87MG cell lines by cell proliferation assay. The internalization of TiONts was studied using Transmission Electron Microscopy (TEM). Finally, the effect of TiONts on cell radiosensitivity was evaluated using clonogenic assay. Cell cycle distribution was evaluated by flow cytometry after DNA labeling. DNA double-stranded breaks were evaluated using γH2AX labeling.
  
  
  RESULTS
  Cells internalized TiONts through the possible combination of endocytosis and diffusion with no cytotoxicity. Clonogenic assays showed that cell lines incubated with TiONts were radiosensitized with a decrease in the SF2 parameter for both SNB-19 and U87MG cells. TiONts decreased DNA repair efficiency after irradiation and amplified G2/M cell-cycle arrest.
  
  
  CONCLUSIONS
  Our results indicated that further development of TiONts might provide a new useful tool for research and clinical therapy in the field of oncology.
authors: Radiotherapy Department, Centre Georges-François Leclerc, Dijon, France.
authors: C
authors: C
authors: Mirjolet
authors: A L
authors: AL
authors: Papa
authors: G
authors: G
authors: Créhange
authors: O
authors: O
authors: Raguin
authors: C
authors: C
authors: Seignez
authors: C
authors: C
authors: Paul
authors: G
authors: G
authors: Truc
authors: P
authors: P
authors: Maingon
authors: N
authors: N
authors: Millot
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage; D005909:Glioblastoma / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D043942:Nanotubes; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014025:Titanium / Q000494:pharmacology*
chemical_list: D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium
keywords: Cytotoxicity; Glioblastoma; Internalization; Radiosensitization; Titanate nanotubes