Enhancing the radio sensitivity of prostate cancer using RALA Gold nano-complexes

Abstract

Radiotherapy(RT) is used with curative intent for the treatment of locally advanced or oligometastatic prostate cancer(PCa). Many patients respond well to RT, however, normal tissue toxicity limits clinical potential. In PCa there is a distinct therapeutic window between normal and malignant tissue, providing an opportunity to exploit for therapeutic gain. This thesis explored ways to improve the use of RT through the application of radiosensitisers, with particular focus on the use of gold nanoparticles (AuNP). AuNP are effective radiosensitisers, however, clinical translation is impeded by short systemic circulation, poor stability and target cell uptake. This thesis employs the cell penetrating peptide RALA to enhance AuNP cell internalisation and in turn radiosensitivity of PCa. RALA-AuNP have undergone extensive characterisation following synthesis, proving optimal for in vitro and in vivo application. Significant improvements in cell uptake and localisation of AuNP have been presented. At the time of writing this thesis includes the first work to definitively confirm Au uptake into the nucleus. Most importantly RALA-AuNP induced significant radiosensitisation at both research and clinically relevant energies at Au concentrations several orders of magnitude lower than previous literature. As such, the findings within this thesis extend our knowledge of radiosensitisers, in particular highlighting the clinical radiosensitising potential of gold nanoparticles.

Date of Award	Jul 2020
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Northern Ireland Department for the Economy
Supervisor	Helen McCarthy (Supervisor) & Jonathan Coulter (Supervisor)