Abstract
Gold nanoparticle (GNP) enhanced proton therapy is a promising treatment concept offering increased therapeutic effect. It has been demonstrated in experiments which provided indications that reactive species play a major role. Simulations of the radiolysis yield from GNPs within a cell model were performed using the Geant4 toolkit. The effect of GNP cluster size, distribution and number, cell and nuclear membrane absorption and intercellular yields were evaluated. It was found that clusters distributed near the nucleus increased the nucleus yield by 91% while reducing the cytoplasm yield by 7% relative to a disperse distribution. Smaller cluster sizes increased the yield, 200 nm clusters had nucleus and cytoplasm yields 117% and 35% greater than 500 nm clusters. Nuclear membrane absorption reduced the cytoplasm and nucleus yields by 8% and 35% respectively to a permeable membrane. Intercellular enhancement was negligible. Smaller GNP clusters delivered near sub-cellular targets maximise radiosensitisation. Nuclear membrane absorption reduces the nucleus yield, but can damage the membrane providing another potential pathway for biological effect. The minimal effect on adjacent cells demonstrates that GNPs provide a targeted enhancement for proton therapy, only effecting cells with GNPs internalised. The provided quantitative data will aid further experiments and clinical trials.
Highlights
Radiotherapy is a modality commonly used in the treatment of cancer
Clusters near nucleus increased nucleus yield by 91% while reducing cytoplasm yield by 7% compared to a disperse distribution
The nucleus yield is increased by 91% by having Gold nanoparticle (GNP) clusters within 1 μm of the nuclear membrane instead of being distributed within a larger region of the cytoplasm
Summary
Radiotherapy is a modality commonly used in the treatment of cancer. Proton therapy has advantages over conventional megavoltage photon therapy. As an incident proton passes through a medium and loses energy, the proton slows down and the rate of energy loss increases producing a peak in energy deposition prior to the proton stopping known as the Bragg peak. The primary advantage of proton therapy over conventional photon therapy is the superior sparing of healthy tissue. In proton therapy it is possible, by selecting the incident proton energies, to distribute Bragg peaks throughout the target volume. This enables the delivery of a highly conformal dose to the target volume while significantly sparing healthy tissue around the target volume
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