Gold Nanoparticle Enhanced Proton Therapy: Monte Carlo Modeling of Reactive Species' Distributions Around a Gold Nanoparticle and the Effects of Nanoparticle Proximity and Clustering.

Peukert Peukert,Bezak Bezak,Douglass Douglass,Kempson Kempson

doi:10.3390/ijms20174280

Abstract

Gold nanoparticles (GNPs) are promising radiosensitizers with the potential to enhance radiotherapy. Experiments have shown GNP enhancement of proton therapy and indicated that chemical damage by reactive species plays a major role. Simulations of the distribution and yield of reactive species from 10 ps to 1 µs produced by a single GNP, two GNPs in proximity and a GNP cluster irradiated with a proton beam were performed using the Geant4 Monte Carlo toolkit. It was found that the reactive species distribution at 1 µs extended a few hundred nm from a GNP and that the largest enhancement occurred over 50 nm from the nanoparticle. Additionally, the yield for two GNPs in proximity and a GNP cluster was reduced by up to 17% and 60% respectively from increased absorption. The extended range of action from the diffusion of the reactive species may enable simulations to model GNP enhanced proton therapy. The high levels of absorption for a large GNP cluster suggest that smaller clusters and diffuse GNP distributions maximize the total radiolysis yield within a cell. However, this must be balanced against the high local yields near a cluster particularly if the cluster is located adjacent to a biological target.

Highlights

Radiation therapy is a commonly used modality in the treatment of cancer
The simulations performed in this work modeled the spatial distribution of reactive species around Gold nanoparticles (GNPs) over time with a full 3D analysis of the yield distributions and enhancement performed for the first time
When combined with the increased radiolysis enhancement ratio at further distances from the nanoparticle this offered a promising pathway for enhancing biological effect at greater ranges

Summary

Introduction

Radiosensitizers, agents, which increase the biological effect of radiation, which are preferentially delivered to tumor tissue, are being examined as a promising method to improve radiation therapy treatment outcomes [1]. The high probability for incident radiation to interact within the dense GNP increases the proportion of the radiation’s energy deposited in the local environment of the GNP. GNPs preferentially accumulate in tumor tissue passively via the enhanced permeation and retention effect (EPR) [2,3] causing an increase in the proportion of dose deposited within the tumor tissue. GNPs were thought to only be an effective radiosensitizer for radiation types with interactions with a strong dependence on Z such as photoelectric interactions for kV photons and pair production interactions for photons of megavoltage (MV) energies. As discussed below, sensitization has been observed for protons

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Discussion

Conclusion