Enhancement of radiation effects by gold nanoparticles for superficial radiation therapy

doi:10.1016/j.nano.2009.01.014

Nanomedicine: Nanotechnology, Biology and Medicine

Volume 5, Issue 2, June 2009, Pages 136-142

https://doi.org/10.1016/j.nano.2009.01.014 Get rights and content

Abstract

Iodinated contrast agents, which are routinely used to improve contrast in x-ray diagnostic radiography, have been successfully proven to enhance radiation effects in kilovoltage x-ray radiation therapy beams. The studies determined the influence of iodine on the level of radiation biotoxicity to cells as an indicator of the radiation dose enhancement. The use of other high-atomic-number materials such as gold nanoparticles (AuNPs) may also provide advantages in terms of radiation dose enhancement. In this work AuNPs have been used for the enhancement of radiation effects on bovine aortic endothelial cells of superficial x-ray radiation therapy and megavoltage electron radiation therapy beams. Results reveal an increase of cell damage with increasing concentration of AuNPs. At 1 mM concentration of AuNPs, enhancement of radiation peaked at 25 times for a kilovoltage x-ray beam. AuNPs showed similar effects on electron beams but to a lesser extent. This study showed that AuNPs can be used to enhance the effect of radiation doses from kilovoltage x-ray radiation therapy and megavoltage electron radiation therapy beams. In the prevailing clinical circumstances, wherein radiation therapy dose is constrained by normal tissue tolerance, this enhancement could in the future be used to improve local control in superficial x-ray treatments, megavoltage electron beam radiation therapy, microbeam radiation therapy, and intraoperative irradiation using kilovoltage x-rays or megavoltage electron beams. Moreover, the value of this work also stems from the fact that the damage to the endothelial cells lining the highly vasculature structure of tumors deprives tumors of their oxygen and nutrients supply and enhances the efficiency of radiation therapy treatment, where it has been proven that more of the AuNPs injected into animals ends up into the blood than in the tumor.

Section snippets

Preparation of AuNPs for experimental use

The spherical AuNPs (1.9 nm) were obtained from Nanoprobes Inc. (Yaphank, New York). These were washed with Dulbecco's modified Eagle's medium (DMEM; Sigma-Aldrich, St Louis, Missouri) and then filtered through a 0.22-μm hydrophilic polysulfonic membrane syringe bacterial filter (Sartorius, Göttingen, Germany). The filtrate was diluted with complete medium to the required concentration.

Cell culture techniques and cell viability assay

BAECs were cultured in DMEM and supplemented with l-glutamine (Sigma-Aldrich), 10% fetal calf serum

Uptake of spherical AuNPs by BAECs

Study of the cell uptake reveals that the AuNPs were internalized before irradiation. Confocal microscopy of cells exposed to AuNPs is shown in Figure 1, which shows that the AuNPs were clustered in the cytoplasm. There was no significant difference between images of different AuNP concentrations observed in the cells, because the AuNPs always clustered together inside the cells. Observation using confocal microscopy showed that AuNPs were fully internalized after 24 hours of exposure.

Cytotoxicity of AuNPs

Initial

Discussion

We have found that incubation of BAECs with AuNPs for about 24 hours leads to the internalization by the cells of most of the AuNPs, as shown in Figure 1. This is in agreement with the findings documented in other studies.¹⁵ However, the number of AuNPs being taken up into the cells has been found to be dependent on the size of AuNPs.¹⁶ In this study 1.9-nm AuNPs were used; however, it has been reported that optimal uptake occurs with 50-nm-diameter spherical AuNPs.¹⁶

Our results indicate that

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Gold Nanoparticles: Clinical Nanomedicine, Radiation OncologyEnhancement of radiation effects by gold nanoparticles for superficial radiation therapy

Abstract

Section snippets

Preparation of AuNPs for experimental use

Cell culture techniques and cell viability assay

Uptake of spherical AuNPs by BAECs

Cytotoxicity of AuNPs

Discussion

Acad Radiol

Int J Radiat Oncol Biol Phys

Nanomedicine

Nucl Instrum Methods

Radiation dose enhancement in tumors with iodine

Med Phys

Dose distributions using kilovoltage x-rays and dose enhancement from iodine contrast agents

Phys Med Biol

Tumour dose enhancement using modified megavoltage photon beams and contrast media

Phys Med Biol

Synchrotron radiation based experimental determination of the optimal energy for cell radiotoxicity enhancement following photoelectric effect on stable iodinated compounds

Br J Cancer

Iodinated contrast agents as radiosensitisers

Br J Radiol

Iodine contrast medium sensitizes cultured mammalian cells to x rays but not to γ rays

Radiat Res

The use of gold nanoparticles to enhance radiotherapy in mice

Phys Med Biol

Gold nanoparticles: a new x-ray contrast agent

Br J Radiol

Gold Nanoparticles: Clinical Nanomedicine, Radiation Oncology
Enhancement of radiation effects by gold nanoparticles for superficial radiation therapy