Unraveling the cell-type dependent radiosensitizing effects of gold through the development of a multifunctional gold nanoparticle

James R. Nicol, Emma Harrison, Shannon M. O'Neill, Dorian Dixon, Helen O. McCarthy, Jonathan A. Coulter

Research output: Contribution to journalArticle

4 Citations (Scopus)
39 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)439-449
Number of pages11
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number2
Early online date2 Dec 2017
DOIs
Publication statusPublished - 1 Feb 2018

Keywords

  • DNA damage
  • Endocytosis
  • Gold nanoparticles
  • Radiosensitization
  • Reactive oxygen species

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