title: Cisplatin-tethered gold nanospheres for multimodal chemo-radiotherapy of glioblastoma.
abstract: Glioblastoma multiforme (GBM) remains the most aggressive and challenging brain tumour to treat. We report the first successful chemo-radiotherapy on patient derived treatment resistant GBM cells using a cisplatin-tethered gold nanosphere. After intracellular uptake, the nanosphere effects DNA damage which initiates caspase-mediated apoptosis in those cells. In the presence of radiation, both gold and platinum of cisplatin, serve as high atomic number radiosensitizers leading to the emission of ionizing photoelectrons and Auger electrons. This resulted in enhanced synergy between cisplatin and radiotherapy mediated cytotoxicity, and photo/Auger electron mediated radiosensitisation leading to complete ablation of the tumour cells in an in vitro model system. This study demonstrates the potential of designed nanoparticles to target aggressive cancers in the patient derived cell lines providing a platform to move towards treatment strategies.
authors.affiliation: Nanoscience Centre, Department of Engineering, University of Cambridge, Cambridge CB3 0FF, UK. mew10@cam.ac.uk.
authors.forename: Sonali
authors.initials: S
authors.lastname: Setua
authors.forename: Myriam
authors.initials: M
authors.lastname: Ouberai
authors.forename: Sara G
authors.initials: SG
authors.lastname: Piccirillo
authors.forename: Colin
authors.initials: C
authors.lastname: Watts
authors.forename: Mark
authors.initials: M
authors.lastname: Welland
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry* / Q000633:toxicity; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006046:Gold / Q000737:chemistry*; D006657:Histones / Q000378:metabolism; D006801:Humans; D054118:Nanospheres / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D011838:Radiation-Sensitizing Agents / Q000737:chemistry* / Q000633:toxicity
chemical_list: D006657:Histones; D011838:Radiation-Sensitizing Agents; D006046:Gold; D011094:Polyethyleneimine; D020169:Caspases; D002945:Cisplatin