Abstract

Alexandra G. Vaideanua, Sonali Setuaa, Myriam Ouberaia, Colin Wattsb, Mark Wellanda, aNanoscience Centre, Department of Engineering, University of Cambridge, bJohn van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge

Glioblastoma multiforme is one of the most aggressive types of cancer. Despite current therapies and standard care patients survive on average 14 months after diagnosis. The aim of our work is to demonstrate the efficacy of a multimodal nanotechnology based on gold nanoparticles in killing glioblastoma cells in human tissue derived cell lines in vitro. We have showed previously1 the synergistic effect of chemotherapy and radiotherapy in a construct based on spherical gold nanoparticles coated with mercaptoundecanoic acid (MUA) to which we attached cis-platinum drug. The increased radiosensitization due to the gold atoms and the delivery of cis-platinum to the tumour cells resulted in a decreasing trend in the recurrence and survival of the cell lines tested. To further improve the technology we have used a modified construct in which we replace the MUA coating with a polyethyleneglycol (PEG) linker. This improved the uptake of nanoparticles via an enhanced permeability retention effect facilitated by the leaky tumour vasculature and as a consequence of reduced interaction of PEG shielded carriers with opsonins. Further strategies in maximizing the efficiency of the system include the attachment of a tumour homing peptide, GRGDR , to specifically target receptors at the surface of glioblastoma cells. The end goal of this work is to validate these findings via in vivo mouse models and to ultimately submit this technology for clinical trials.

1. Setua, S., Ouberai, M., Piccirillo, S. G., Watts, C. & Welland, M. Cisplatin-tethered gold nanospheres for multimodal chemo-radiotherapy of glioblastoma. Nanoscale 6, 10865–10873 (2014)