Cisplatin-tethered gold nanospheres for multimodal chemo-radiotherapy of glioblastoma

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 damag...

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Bibliographic Details
Published in:Nanoscale 2014-09, Vol.6 (18), p.10865-10873
Main Authors: Setua, Sonali, Ouberai, Myriam, Piccirillo, Sara G, Watts, Colin, Welland, Mark
Format: Article
Language:English
Subjects:
Ablation
Apoptosis - drug effects
Apoptosis - radiation effects
Atomic properties
Augers
Caspases - metabolism
Cell Line, Tumor
Cisplatin - chemistry
Cisplatin - toxicity
DNA Damage - drug effects
DNA Damage - radiation effects
Gamma Rays
Glioblastoma - metabolism
Glioblastoma - pathology
Gold
Gold - chemistry
Histones - metabolism
Humans
Nanospheres
Nanospheres - chemistry
Nanostructure
Patients
Polyethyleneimine - chemistry
Radiation-Sensitizing Agents - chemistry
Radiation-Sensitizing Agents - toxicity
Tumours
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Summary: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.
ISSN:2040-3364
2040-3372
DOI:10.1039/c4nr03693j