Fig. 4: Evaluation of nanodiamonds as proton radiosensitizers.

a Histogram showing the distribution of nanodiamond-to-nucleus distance that was experimentally measured within 12 HepG2 cells. The magnified inset indicates that zero nanoparticles were found within 457 nm of the nuclear boundary. b Plausible mechanisms of nanodiamond-mediated proton radiosensitization in damaging nuclear DNA. Secondary electrons can be induced by the 2-MeV protons when they penetrate a nanodiamond. The secondary electrons that emanate from the nanodiamond, as well as subsequent generations of induced electrons, can either damage nuclear DNA directly or ionize intracellular water molecules in producing reactive oxygen species (ROS) to react with nuclear DNA indirectly. c Calculated energy distribution of the secondary electrons escaping the nanodiamond at its surface, simulated with Geant4-DNA. d Image showing range distributions of the secondary electrons in liquid water, simulated with Geant4-DNA. Note that we assumed the protons travel only within the nanodiamond (100 nm diameter). Scale bar, 100 nm. e Image showing range distributions of hydroxyl radicals (•OH) in liquid water, simulated with Geant4-DNA. Scale bar, 100 nm. f Measurement of the number of hydroxyl radicals and secondary electrons per proton impact as a function of their distances from the nanodiamond-surface. Note that only those traveling more than 457 nm (the minimum nanodiamond-to-nucleus distance determined in a) were taken into account.