SummaryWith several gold nanoparticle based therapies currently undergoing clinical trials, these treatments may soon be in the clinic as novel anti-cancer agents. Gold nanoparticles are the subject of a wide ranging international research effort with preclinical studies underway for multiple applications including photoablation, diagnostic imaging, radiosensitisation and multi-functional drug delivery vehicles. These applications require an increasingly complex level of surface modification in order to achieve efficacy and limit off-target toxicity. This review will discuss the main obstacles in relation to surface functionalization and the chemical approaches commonly utilised. Finally we review a range of recent pre-clinical studies that aim to advance gold nanoparticle treatments towards the clinic.
The field of high atomic number nanoparticle radiosensitising agents is reviewed. After a brief discussion of the new mode of physicochemical action implied by irradiation of high atomic number nanoparticles embedded in biological systems, a series of exemplars are discussed.Silver-, gallium-and gold-based nanoparticles are discussed in order of increasing atomic number with functionalization strategies being outlined. In-vitro and in-vivo evidence for radioenhancement and the mechanisms attributed to the increased biological effect are discussed.
The radiosensitizing 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-functionalized with two biologically derived peptides designed to enhance endocytosis and promote endosomal escape, thus maximizing intracellular AuNP surface area. In summary, these investigations demonstrate restored AuNP internalization using the co-functionalized preparation that generated significant radiosensitization, 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 radiosensitizing efficacy.
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