Unravelling the cell-type dependent radiosensitising effects of gold through the development of a multifunctional gold nanoparticle

The radiosensitising efficacy of gold is well established, however, there remain several significant barriers to the successful clinical translation of nano-sized gold particles (AuNPs). These barriers include: retaining stability in relevant biological sera, demonstrating effectiveness at clinically relevant AuNP concentrations and identifying the biological context where significant benefit is most likely to be achieved. Herein we have developed a AuNP preparation, stress-tested to provide effective protection from salt and serum mediated agglomeration. Furthermore, the core AuNP is co-functionalised with two biologically derived peptides designed to enhance endocytosis and promote endosomal escape, thus maximising intracellular AuNP surface area. In summary, these investigations demonstrate restored AuNP internalisation using the co-functionalised preparation that generated significant radiosensitisation, in both in vitro and in vivo models, at clinically viable treatment concentrations. Furthermore, we have identified an underpinning biological mechanism in the inherent radical scavenging capacity that could be used to predict radiosensitising efficacy.