Gold nanoparticles for cancer radiotherapy: a review

Abstract

Radiotherapy is currently used in around 50% of cancer treatments and relies on the deposition of energy directly into tumour tissue. Although it is generally effective, some of the deposited energy can adversely affect healthy tissue outside the tumour volume, especially in the case of photon radiation (gamma and X-rays). Improved radiotherapy outcomes can be achieved by employing ion beams due to the characteristic energy deposition curve which culminates in a localised, high radiation dose (in form of a Bragg peak). In addition to ion radiotherapy, novel sensitisers, such as nanoparticles, have shown to locally increase the damaging effect of both photon and ion radiation, when both are applied to the tumour area. Amongst the available nanoparticle systems, gold nanoparticles have become particularly popular due to several advantages: biocompatibility, well-established methods for synthesis in a wide range of sizes, and the possibility of coating of their surface with a large number of different molecules to provide partial control of, for example, surface charge or interaction with serum proteins. This gives a full range of options for design parameter combinations, in which the optimal choice is not always clear, partially due to a lack of understanding of many processes that take place upon irradiation of such complicated systems. In this review, we summarise the mechanisms of action of radiation therapy with photons and ions in the presence and absence of nanoparticles, as well as the influence of some of the core and coating design parameters of nanoparticles on their radiosensitisation capabilities.

Keywords: Gold nanoparticles; Nanomedicine; Radiosensitisation.

Fig. 1

Illustration of mechanisms of radiation damage. Both photon and ion radiation (red wiggly and straight lines, respectively) may directly damage DNA (marked with yellow stars) or other parts of the cell, such as mitochondria (damage not shown), as well as ionise the medium thereby producing radicals and other reactive species (represented here by the $·$OH radical) as well as secondary electrons, which can cause indirect damage after diffusion (red stars). Secondary electrons may also react with the medium to further increase the number of radicals. See text for further details

Fig. 2

Illustration of mechanisms of radiation damage in the presence of nanoparticles. In addition to the direct and indirect damage (yellow and red stars, respectively) to DNA or other parts of the cell (a), the incident radiation may also interact with NPs (b) (illustrated by dashed, wiggly arrows) and induce the emission of secondary electrons which can then react with the medium to increase the production of radicals and other reactive species (like $·$OH radicals); secondary electrons produced by the radiation or by NPs may also induce further electron emission from NPs. c All the secondary species may diffuse and damage other parts of the cell (like mitochondria). See text for further details

Fig. 3

Illustration of PEG-coated AuNPs. Output from simulation of 1.4 nm AuNPs coated with a 32 and b 60 PEG molecules. Details in Ref. Haume et al. (2016)