4.8 Article

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

Journal

NANOSCALE
Volume 6, Issue 18, Pages 10865-10873

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/c4nr03693j

Keywords

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Funding

  1. Cambridge Commonwealth, European and International Trust's research fellowship
  2. Biotechnology and Biological Sciences Research Council (BBRSC) [BB/H003843/1]
  3. European Commission
  4. BBSRC [BB/H003843/1] Funding Source: UKRI
  5. Biotechnology and Biological Sciences Research Council [BB/H003843/1] Funding Source: researchfish
  6. Cancer Research UK [16700] Funding Source: researchfish

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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.

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