title: In vitro and in vivo radiosensitization induced by hydroxyapatite nanoparticles.
abstract: BACKGROUND
  Previous study showed that hydroxyapatite nanoparticles (nano-HAPs) inhibited glioma growth in vitro and in vivo; and in a drug combination, they could reduce adverse reactions. We investigated the possible enhancement of radiosensitivity induced by nano-HAPs.
  
  
  METHODS
  In vitro radiosensitization of nano-HAPs was measured using a clonogenic survival assay in human glioblastoma U251 and breast tumor brain metastatic tumor MDA-MB-231BR cells. DNA damage and repair were measured using γH2AX foci, and mitotic catastrophe was determined by immunostaining. The effect of nano-HAPs on in vivo tumor radiosensitivity was investigated in a subcutaneous and an orthotopic model.
  
  
  RESULTS
  Nano-HAPs enhanced each cell line's radiosensitivity when the exposure was 1 h before irradiation, and they had no significant effect on irradiation-induced apoptosis or on the activation of the G2 cell cycle checkpoint. The number of γH2AX foci per cell was significantly large at 24 h after the combination modality of nano-HAPs + irradiation compared with single treatments. Mitotic catastrophe was also significantly increased at an interval of 72 h in tumor cells receiving the combined modality compared with the individual treatments. In a subcutaneous model, nano-HAPs caused a larger than additive increase in tumor growth delay. In an orthotopic model, nano-HAPs significantly reduced tumor growth and extended the prolongation of survival induced by irradiation.
  
  
  CONCLUSIONS
  These results show that nano-HAPs can enhance the radiosensitivity of tumor cells in vitro and in vivo through the inhibition of DNA repair, resulting in an increase in mitotic catastrophe.
authors.affiliation: Department of Neurosurgery, Shanghai 3rd People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201900, China. shenghuachu@126.com
authors.forename: Sheng-Hua
authors.initials: SH
authors.lastname: Chu
authors.forename: Surya
authors.initials: S
authors.lastname: Karri
authors.forename: Yan-Bin
authors.initials: YB
authors.lastname: Ma
authors.forename: Dong-Fu
authors.initials: DF
authors.lastname: Feng
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001672:Biocompatible Materials / Q000494:pharmacology; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D017886:Durapatite / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014965:X-Rays
chemical_list: D001672:Biocompatible Materials; C468783:H2AX protein, human; D006657:Histones; D011838:Radiation-Sensitizing Agents; D017886:Durapatite
keywords: glioblastoma; hydroxyapatite nanoparticles; irradiation; radiosensitization; rain metastatic tumor