Why gold nanoparticles sensitize cells in megavoltage photon beams
In plain words
At the high photon energies used in the clinic, gold should add almost no extra absorbed dose, yet experiments report clear extra cell killing. The source of the extra effect is unknown.
Precise statement
For gold nanoparticles of 2 to 50 nm diameter at intracellular mass fractions of 0.1 to 1 percent, irradiated by 6 MV photon beams, the macroscopic dose enhancement computed by Monte Carlo transport is of order 1 percent or less, while reported sensitizer enhancement ratios at 10 percent survival range from about 1.1 to 1.5. Identify the mechanism, or combination, that accounts for the excess: nanometre-scale dose heterogeneity from photoelectron and Auger emission near the particle, surface-catalysed radical production, or biological pathways such as mitochondrial or cell-cycle effects. An answer is a model that predicts the enhancement ratio as a function of particle size, coating, location and beam energy without refitting.
What would settle it
Experiments that vary particle location (membrane, cytoplasm, nucleus), coating and beam energy at fixed gold mass, with radical-yield probes, compared against track-structure calculations at nanometre resolution.
Status in the literature
Reviews through the early 2020s report that physical dose enhancement alone does not reproduce megavoltage results and no mechanism has been agreed.