Glioblastoma is a heterogeneous disease with multiple genotypic origins. Despite treatment protocols such as surgery, radiotherapy and chemotherapy, the prognosis for patients remains poor. This study investigates the cytotoxic and radiation dose-enhancing and radiosensitizing ability of five rare earth oxide nanoparticles, in two different immortalized mammalian cell lines; U-87 MG and Mo59K. Significant cytotoxicity was observed in U-87 MG cells when exposed to Nd 2 O 3 and La 2 O 3. Autophagy was also detected in cells after incubation with Nd 2 O 3. Radiosensitization was observed in U-87 MG when incubated with Gd 2 O 3 , CeO 2-Gd and Nd 2 O 3 :Si. Importantly, these elements did not cause any intrinsic toxicity in the absence of irradiation and so could be considered biocompatible. The Gd 2 O 3 and CeO 2-Gd nanoparticles were also seen to generate ROS in U-87 MG cells after irradiation. Furthermore, the Mo59K and U-87 MG cells responded very differently to exposure to the rare earth nanoparticles. This may indicate the importance of the genotype of cells in the successful use of rare earth oxides for treatment.

Dysregulation of iron metabolism is a common characteristic of cancer cells. The rapid proliferation of the tumour cells means that there is an increased dependence upon iron compared to healthy cells. Chelation of iron can be undertaken with a number of different compounds, however, simply lowering systemic iron levels to control tumour growth is not possible since iron is essential for cellular metabolism in the rest of the body. Nanoparticulate iron chelators could overcome this difficulty by targeting to the tumour either by the passive enhanced permeation and retention effect, or by targeting ligands on the surface. Nanoparticles were prepared from melanin, which is a naturally occurring pigment that is widely distributed within the body, but that can chelate iron. The prepared nanoparticles were shown to be ~220 nm, and could adsorb 16.45 mmoles iron/g melanin. The nanoparticles showed no affect on control fibroblast cells at a concentration of 200 μM, whereas the immortalised cancer cell lines showed at least 56% reduction in cell growth. At a concentration of 1 mM melanin nanoparticles the cell growth could be reduced by 99% compared to the control. The nanoparticles also show no significant haemotoxicity, even at concentration of 500 μM. Melanin nanoparticles are therefore a viable prospect for destroying cancer cells via iron starvation.