Gold nanoparticle enhanced proton therapy: A Monte Carlo simulation of the effects of proton energy, nanoparticle size, coating material, and coating thickness on dose and radiolysis yield

Abstract

Purpose Radiosensitizer enhanced radiotherapy provides the possibility of improved treatment outcomes by preferentially increasing the effectiveness of radiation within the tumor. Proton therapy offers improved sparing of tissue distal of the tumor along the beam path and reduced integral dose compared to conventional photon therapy. The combination of proton therapy with radiosensitizers offers the potential for an enhanced therapy with increased effect within the tumor and low integral dose. The simulations performed in this work determine the effect of nanoparticle characteristics and proton energy on the nanoscale dose and radiolysis yield enhancement for a single gold nanoparticle irradiated with a proton beam. This data can be used to determine optimal nanoparticle characteristics to enhance proton therapy. Methods A two‐stage Monte Carlo simulation was performed using Geant4. In the first stage of the simulation, the physical interactions of protons within a gold nanoparticle were modeled and the secondary electrons escaping the nanoparticle's surface were scored in a phase space file. In the second stage of the simulation, the phase space file was used as an input to model the physical interactions of the secondary electrons in water and the resulting production and chemical interactions of reactive species. By comparing a gold nanoparticle with an equivalent water nanoparticle, the nanoscale enhancement of dose and radiolysis yield was calculated. Results A large nanoscale enhancement of both the dose and radiolysis yield of up to a factor of 11 due to gold nanoparticles was found for most simulated conditions. For 50 nm gold nanoparticles, a large enhancement factor of 9–11 was observed for high proton energies; however, the enhancement was reduced for proton energies below 10 MeV. For 5 MeV incident protons, it was found that the enhancement factor was approximately 9 for gold nanoparticles of sizes 5–25 nm with a reduction in enhancement observed for nanoparticle sizes outside this range. Additionally, it was found that larger nanoparticle sizes resulted in greater total energy deposition and radiolysis yields per proton flux but with reduced efficiency per nanoparticle mass. It was observed that a large loss of enhancement occurred for thick nanoparticle coatings. However, for polyethylene glycol (PEG) coatings, coating density had a minimal effect on enhancement. Conclusions A large enhancement in dose and radiolysis yield was observed. However, the low‐energy secondary electrons produced within the gold for lower energy protons are susceptible to self‐absorption and result in the loss of enhancement observed for larger nanoparticles and thicker coatings. The radiolysis yield and dose increase with nanoparticle size; however, the yield and dose per gold mass decrease due to self‐absorption. Therefore, an intermediate nanoparticle size of approximately 10–25 nm maximizes both the radiolysis yield and dose as well as the enhancement. Coatings should be kept to the minimum effective thickness to limit ...

Mechanisms of nanoparticle radiosensitization

“…This is likely due to passivation of the solid liquid interfacial catalysis of radicals, and/or absorption of secondary electrons emitted from the nanoparticle within the coating layer. The latter mechanism was supported by data showing a decrease in yield with increasing coating atoms, and has been further supported by Monte Carlo modeling (Peukert et al, 2020). Furthermore, Gilles et al showed that the GNPs were highly effective in producing ROS that caused plasmid DNA damage, encouraging for mechanistically understanding radiosensitization.…”

“…GNP coating composition and thickness has been shown to play a major role in reducing radiolysis of water surround nanoparticles due to the inability of secondary electrons generated in the GNP being able to escape through the coating, as shown theoretically (Peukert, Kempson, Douglass, & Bezak, 2020) and experimentally (Le Goas et al, 2019). In the absence of radiation, protein corona has also been shown to reduce generation of ROS from TiO 2 nanoparticles by passivating the catalytic capability at the NP‐liquid interface (Runa, Lakadamyali, Kemp, & Payne, 2017).…”

Modelling Spatial Scales of Dose Deposition and Radiolysis Products from Gold Nanoparticle Sensitisation of Proton Therapy in A Cell: From Intracellular Structures to Adjacent Cells

“…The nanoparticle geometry consisted of clusters of 15 nm nanoparticles constructed from in vitro measurements of GNP clustering within HeLa cells [ 16 ]. Bare 15 nm GNPs were chosen to be modelled as a previous optimisation study by the authors [ 28 ] showed that 15 nm is an optimal GNP size to maximise enhancement, providing a balance of gold mass and limited self-absorption of secondary electrons within the GNPs. The study also showed that thicker nanoparticle coatings reduced the enhancement by absorbing secondary electrons produced within the gold core preventing their contribution to the dose and reactive species yield outside of the nanoparticle.…”

“…In previous work by the current authors, an optimisation study of GNP characteristics was performed to maximise the radiolysis yield enhancement [ 28 ]. This study was the first application of the simulation framework developed by the authors using the Geant4 Monte Carlo toolkit [ 24 , 25 , 26 ].…”

“…In this work, the simulation framework previously developed by the authors [ 28 , 29 ] was used to model the enhancement from GNP distributions with a cell model. The cell model simulations were used to investigate (a) the effect of the size, distribution and number of GNP clusters on the absolute radiolysis yield within cellular components, (b) the effect of the reactive species permeability of the nuclear and cellular membranes on the reactive species yield as well as the distribution of reactive species stopped within the membrane and (c) the reactive species yield in a second cell adjacent to a cell containing GNPs from secondary electrons emitted from the GNPs for various cell separations.…”