GOLD NANOPARTICLE ENHANCED PROTON THERAPY

Abstract

Radiation therapy uses high doses of radiation to kill or delay the growth of the malignant cells in a tumour. Its success is linked with the ability of delivering a high radiation dose to the tumour, while sparing the healthy tissues surrounding the tumour. Unfortunately, for a specific treatment setup the radiation beam has to pass through normal tissues, depositing unnecessary dose. Healthy tissues have limited tolerance to radiation, compromising the success of the treatment. For this reason, methods that increase the radiation effect in the tumour while the radiation dose to the healthy tissues is within tolerance are highly desired. In this direction, studies have shown that the presence of gold nanoparticles in the irradiated tumour radiosensitizes the malignant cells, rendering the radiation more harmful. However, the exact mechanisms are not well known and investigations are needed to understand the underlying mechanisms in order to quantify and improve this method. In this thesis the contribution of the physical interaction mechanisms to the radiosensitization effect is investigated. While an in vivo investigation of the physical interactions inside the cell is impossible, Monte Carlo simulations of radiation transport can provide insight into the physical mechanisms. The Geant4 Monte Carlo simulation toolkit was implemented for this purpose. Firstly the effect of the different interaction models on the dose distributions around a gold nanoparticle was assessed. Then a cellular model with detailed DNA structures was implemented after further improvements to include the chemical stage of the radiation action. With this model the physical DNA damage enhancement of a cell loaded with gold nanoparticles was quantified under photon and proton irradiation. The cellular model calculations revealed that the physical DNA damage and dose enhancement in the presence of gold nanoparticles is not significant under proton irradiation. In contrast, under photon irradiation there is an enhancement proportional to the gold nanoparticle content. The finding of the thesis provided concrete data to a growing body of data suggesting that the radiosensitization due to physical interactions is limited, especially in the case of proton irradiations and other mechanisms, biological or chemical, could contribute more to the effect.

Date of Award	1 Aug 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Ranald Mackay (Supervisor), Karen Kirkby (Supervisor) & Mike Merchant (Supervisor)