Angiogenesis plays a key role in
cancer progression, including
transition to the metastatic phase via reactive oxygen
species (ROS)-dependent pathways, among others. Antivascular endothelial
growth factor (VEGF) antibodies have been trialed as an anti-angiogenic
therapy for cancer but are associated with high cost, limited efficacy,
and side effects. Cerium oxide nanoparticles (nanoceria) are promising
nanomaterials for biomedical applications due to their ability to
modulate intracellular ROS. Nanoceria can be produced by a range of
synthesis methods, with chemical precipitation as the most widely
explored. It has been reported that chemical precipitation can fine-tune
primary particle size where a limited number of synthesis parameters
were varied. Here, we explore the effect of temperature, precipitating
agent concentration and rate of addition, stirring rate, and surfactant
concentration on nanoceria primary particle size using a fractional
factorial experimental design approach. We establish a robust synthesis
method for faceted nanoceria with primary particle diameters of 5–6
nm. The nanoceria are not cytotoxic to a human melanoma cell line
(Mel1007) at doses up to 400 μg/mL and are dose-dependently
internalized by the cells. The intracellular ROS level for some cells
that internalized the nanoceria is reduced, which correlates with
a dose-dependent reduction in angiogenic gene expression including
VEGF. These findings contribute to our knowledge of the anti-angiogenic
effects of nanoceria and help to develop our understanding of potentially
new anti-angiogenic agents for combination cancer therapies.