Shape-Driven Response of Gold Nanoparticles to X-rays

Abstract

Radiotherapy (RT) involves delivering X-ray beams to the tumor site to trigger DNA damage. In this approach, it is fundamental to preserve healthy cells and to confine the X-ray beam only to the malignant cells. The integration of gold nanoparticles (AuNPs) in the X-ray methodology could be considered a powerful tool to improve the efficacy of RT. Indeed, AuNPs have proven to be excellent allies in contrasting tumor pathology upon RT due to their high photoelectric absorption coefficient and unique physiochemical properties. However, an analysis of their physical and morphological reaction to X-ray exposure is necessary to fully understand the AuNPs' behavior upon irradiation before treating the cells, since there are currently no studies on the evaluation of potential NP morphological changes upon specific irradiations. In this work, we synthesized two differently shaped AuNPs adopting two different techniques to achieve either spherical or star-shaped AuNPs. The spherical AuNPs were obtained with the Turkevich-Frens method, while the star-shaped AuNPs (AuNSs) involved a seed-mediated approach. We then characterized all AuNPs with Transmission Electron Microscopy (TEM), Uv-Vis spectroscopy, Dynamic Light Scattering (DLS), zeta potential and Fourier Transform Infrared (FTIR) spectroscopy. The next step involved the treatment of AuNPs with two different doses of X-radiation commonly used in RT, namely 1.8 Gy and 2 Gy, respectively. Following the X-rays' exposure, the AuNPs were further characterized to investigate their possible physicochemical and morphological alterations induced with the X-rays. We found that AuNPs do not undergo any alteration, concluding that they can be safely used in RT treatments. Lastly, the actin rearrangements of THP-1 monocytes treated with AuNPs were also assessed in terms of coherency. This is a key proof to evaluate the possible activation of an immune response, which still represents a big limitation for the clinical translation of NPs.

Keywords: X-rays; gold nanoparticles; medical physics; nanoparticle synthesis; physicochemical properties; radiotherapy.

Figure 1

Water-equivalent phantom housing AuNP samples.

Figure 2

(A) Axial, (B) sagittal and (C) coronal images of the dose distribution in the AuNP sample contained in the phantom; (D) view from the accelerator gantry (Beam Eye View—BEV); (E) 3D image of the phantom with the irradiation beam inputs. In the white dashed circle was the isodose curves legend.

Figure 3

TEM acquisitions of AuNPs obtained by Turkevich–Frens method (a), Au seeds (b) and the relative SAED patterns (c,d). Size distribution of Turkevich–Frens AuNPs (e) and AuNP seeds obtained with ImageJ software (f).

Figure 4

TEM acquisitions of the AuNSs after 6 and 9 h of synthetic approach (a,c) and relative SAED pattern (b,d). TEM images of AuNSs obtained after 12 h of reaction time at different magnifications (e–i). SAED pattern of AuNSs (j).

Figure 5

Representative image of the dimensional analysis of three AuNS components, i.e., the length h of the branches, the core-tip distance R and the core diameter r (a); size distributions of the components h, R and r, (b–d), respectively, performed with ImageJ software.

Figure 6

Uv-vis spectra of AuNPs obtained with Turkevich–Frens method.

Figure 7

UV-vis spectra of Au seeds (a) and AuNSs after 6 h (b), 9 h (c) and 12 h (d) of reaction.

Figure 8

TEM acquisitions of the Turkevich–Frens AuNPs (a) and AuNSs (b) after 1.8 Gy irradiation dose; TEM acquisitions of the Turkevich–Frens AuNPs (c) and AuNSs (d) after 2 Gy irradiation dose.

Figure 9

UV-vis absorption spectra of AuNPs achieved with Turkevich–Frens method (a) and AuNSs from seed and growth approach (b) after 1.8 Gy X-ray radiation. ATR-FTIR spectra of Turkevich–Frens AuNPs before (black trace) and after (red trace) X-ray irradiation (1.8 Gy) (c) and ATR-FTIR spectra of AuNS samples and growth organic components (d). From top to bottom of (d): non-irradiated AuNSs (black trace), AuNSs after exposure to 1.8 Gy X-ray radiation (red trace), Triton X-100 (blue trace) and ascorbic acid (purple trace). ATR-FTIR spectra were suitably normalized and stacked to enable the easy comparison of qualitative features. The yellow panels in (c,d) outline the spectral regions where the absorption bands due to stretching (ν) vibration modes of specific functional groups can be found.

Figure 10

(a–f) Confocal acquisitions of THP-1 cells treated with 100 uM and 300 uM of AuNSs for 24 h and 48 h. Coherency values applied to confocal acquisitions with ImageJ software (g).