Sensitization of pancreatic cancer cells to radiation by cerium oxide nanoparticle-induced ROS production

Cerium oxide nanoparticles (CONPs) sensitize acidic cancer cells and desensitize neutral normal cells to radiation therapy (RT)-induced hydrogen peroxide accumulation and subsequent cell death in a cell acidity dependent manner. In the absence of CONPs, cancer cells are relatively resistant to RT-induced superoxide accumulation compared to normal cells (compare 2 to 1). In the absence of RT, the acidic cancer cellular environment promotes the superoxide scavenging activity of Ce3 + state of CONPs but blocks the hydrogen peroxide scavenging activity of Ce4 + state of CONPs resulting in the accumulation of hydrogen peroxide, which does not happen to the neutral environment of normal cells (compared 4 to 3). In the presence of CONPs, RT induces even more hydrogen peroxide accumulation in cancer cells presumably by aiding in the switch of the oxidation states of CONPs from Ce4 + to Ce3 + (compare 6 to 4), which does not occur to the neutral environment of normal cells (compared 6 to 5).141