Radiosensitization Effect of Gold Nanoparticles in Proton Therapy

Charnay Cunningham,Monique Engelbrecht,Jacobus Slabbert,Xanthene Miles,Charlot Vandevoorde,Maryna De Kock

doi:10.3389/fpubh.2021.699822

Charnay Cunningham, Monique Engelbrecht + Show 4 more

Open Access

https://doi.org/10.3389/fpubh.2021.699822

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Abstract

The number of proton therapy facilities and the clinical usage of high energy proton beams for cancer treatment has substantially increased over the last decade. This is mainly due to the superior dose distribution of proton beams resulting in a reduction of side effects and a lower integral dose compared to conventional X-ray radiotherapy. More recently, the usage of metallic nanoparticles as radiosensitizers to enhance radiotherapy is receiving growing attention. While this strategy was originally intended for X-ray radiotherapy, there is currently a small number of experimental studies indicating promising results for proton therapy. However, most of these studies used low proton energies, which are less applicable to clinical practice; and very small gold nanoparticles (AuNPs). Therefore, this proof of principle study evaluates the radiosensitization effect of larger AuNPs in combination with a 200 MeV proton beam. CHO-K1 cells were exposed to a concentration of 10 μg/ml of 50 nm AuNPs for 4 hours before irradiation with a clinical proton beam at NRF iThemba LABS. AuNP internalization was confirmed by inductively coupled mass spectrometry and transmission electron microscopy, showing a random distribution of AuNPs throughout the cytoplasm of the cells and even some close localization to the nuclear membrane. The combined exposure to AuNPs and protons resulted in an increase in cell killing, which was 27.1% at 2 Gy and 43.8% at 6 Gy, compared to proton irradiation alone, illustrating the radiosensitizing potential of AuNPs. Additionally, cells were irradiated at different positions along the proton depth-dose curve to investigate the LET-dependence of AuNP radiosensitization. An increase in cytogenetic damage was observed at all depths for the combined treatment compared to protons alone, but no incremental increase with LET could be determined. In conclusion, this study confirms the potential of 50 nm AuNPs to increase the therapeutic efficacy of proton therapy.

Highlights

50% of the patients with malignant tumors receive radiotherapy (RT) as part of their initial cancer treatment [1]
The uptake and localization of the 50 nm AuNPs in CHO-K1 cells was confirmed with inductively coupled mass spectrometry (ICP-MS) and Transmission electron microscopy (TEM) respectively
For the ICP-MS experiments, the cells were exposed to different low concentrations of 50 nm AuNPs (2.5, 5 and 10 μg/ml) for 4 hours, based on concentrations and incubation times that were used in previous studies [36, 55]

Summary

INTRODUCTION

50% of the patients with malignant tumors receive radiotherapy (RT) as part of their initial cancer treatment [1]. The underlying mechanisms that are responsible for the observed radiosensitization effects are not completely understood and there are currently only a limited number of in vitro and in vivo studies combining proton irradiation and AuNPs [33,34,35,36,37,38,39,40,41,42,43] This in vitro study with larger 50 nm AuNPs was designed as a proof of principle to investigate the uptake, cytotoxicity, radiosensitization effect and the potential LET-dependence of this effect, for a high-energy (200 MeV) clinical proton beam

MATERIALS AND METHODS

RESULTS

DISCUSSION

DATA AVAILABILITY STATEMENT