title: Biological modeling of gold nanoparticle enhanced radiotherapy for proton therapy.
abstract: Gold nanoparticles (GNPs) have shown potential as a radiosensitizer for radiation therapy using photon beams. Recently, experimental studies have been carried out using proton beams showing the GNP enhanced responses in proton therapy. In this work, we established a biological model to investigate the change in survival of irradiated cells due to the radiosensitizing effect of gold nanoparticles. Results for proton, megavoltage (MV) photon and kilovoltage (kV) photon beams are compared. For each particle source, we assessed various treatment depths, GNP cellular uptakes and sizes. We showed that kilovoltage photons caused the highest enhancement due to the high interaction probability between GNPs and kV photons. The cell survival fraction can be significantly reduced for both proton and MV photon irradiations if GNPs accumulate in the cell. For instance, the sensitizer enhancement ratio (SER) is 1.33 for protons in the middle of a spread out Bragg peak for 1 µM of internalized 50 nm GNPs. If the GNPs can all be internalized into the cell nucleus, the SER for proton therapy increases from 1.33 to 1.81. The results also show that for the same mass of GNPs in the cells, one can expect the greatest sensitization by smaller GNPs, i.e. a SER of 1.33 for 1 µM of internalized 50 nm GNPs and a SER of 3.98 for the same mass of 2 nm GNPs. We concluded that if the GNPs cannot be internalized into the cytoplasm, no GNP enhancement will be observed for proton treatment. Meanwhile, proton radiotherapy can potentially be enhanced with GNPs if they can be internalized into cells, and especially the cell nucleus.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Lin
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McMahon
authors.forename: Harald
authors.initials: H
authors.lastname: Paganetti
authors.forename: Jan
authors.initials: J
authors.lastname: Schuemann
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D006046:Gold / Q000737:chemistry / Q000528:radiation effects; D053768:Metal Nanoparticles / Q000009:adverse effects / Q000737:chemistry / Q000528:radiation effects*; D008954:Models, Biological; D017785:Photons; D061766:Proton Therapy / Q000379:methods*; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000737:chemistry / Q000528:radiation effects*
chemical_list: D011838:Radiation-Sensitizing Agents; D006046:Gold