Evaluation of cytotoxicity and radiation enhancement using 1.9 nm gold particles: potential application for cancer therapy

Abstract

High atomic number (Z) materials such as gold preferentially absorb kilovoltage x-rays compared to soft tissue and may be used to achieve local dose enhancement in tumours during treatment with ionizing radiation. Gold nanoparticles have been demonstrated as radiation dose enhancing agents in vivo and in vitro. In the present study, we used multiple endpoints to characterize the cellular cytotoxic response of a range of cell lines to 1.9 nm gold particles and measured dose modifying effects following transient exposure at low concentrations. Gold nanoparticles caused significant levels of cell type specific cytotoxicity, apoptosis and increased oxidative stress. When used as dose modifying agents, dose enhancement factors varied between the cell lines investigated with the highest enhancement being 1.9 in AGO-1522B cells at a nanoparticle concentration of 100 μg ml −1 . This study shows exposure to 1.9 nm gold particles to induce a range of cell line specific responses including decreased clonogenic survival, increased apoptosis and induction of DNA damage which may be mediated through the production of reactive oxygen species. This is the first study involving 1.9 nm nanometre sized particles to report multiple cellular responses which impact on the radiation dose modifying effect. The findings highlight the need for extensive characterization of responses to gold nanoparticles when assessing dose enhancing potential in cancer therapy.

First proof of bismuth oxide nanoparticles as efficient radiosensitisers on highly radioresistant cancer cells

“…For each group, the surviving fraction (SF) is determined as the ratio of the PE of the irradiated sample (PE x ) by PE of the non-irradiated control (PE c ): ) and β (Gy -2 ), are indicative of cell radiosensitivity and repair effectiveness, respectively [7]. They are derived from the LQM equation (4): (4) We quantified the degree of dose enhancement introduced by the NPs by means of the Sensitisation Enhancement Ratio (SER), defined as the ratio of doses giving 10% cell surviving fraction.…”

“…Investigations into gold NPs [4][5][6][7] and Platinum [8,9] NPs were performed to quantify the biocompatibility of the proposed nanomaterials.…”

Gold nanoparticles in cancer therapy

“…A study on mice bearing subcutaneous EMT-6 mammary carcinomas showed that not only were AuNPs (1.9 nm in diameter) non-toxic in nature and cleared from the body via the kidneys, they possessed the ability to enhance the effect of X-ray therapy leading to a remarkable survival rate of 86% as opposed to 20% with X-rays alone and 0% with AuNPs alone [59] . However, it is crucial to note that while 1.9 nm AuNPs seem to show potential as radiation enhancing agents, a recent study discovered evidence for acute cytotoxicity, DNA damage and apoptosis mediated by oxidative stress induced by cellular uptake of 1.9 nm AuNPs [60] . There is a need for further understanding of cellular responses to AuNPs when exploring their potential to be used in radiation therapy to cure cancer.…”

Supramolecular nanoscale assemblies for cancer diagnosis and therapy

“…Damage to deoxyribonucleic acid (DNA) caused by radiation leads to size reduction and destruction of tumours [4,205,206]. Therefore, if NPs act as radiopharmaceuticals or radiosensitizers such cancer treatment modality can be significantly improved [4,207]. Metallic NPs can enhance radiation effects by scattering and/or absorbing high-energy electromagnetic waves (X-rays and gamma rays) [57].…”

“…El-Sayed et al reported that the use of EGFR coated AuNPs increased the photothermal therapy effect by 20 times in human oral squamous cell carcinoma HSC3 cells [210]. Several studies have shown increase in absorption of X-rays by AuNPs internalized in cancer cells [207,211,212]. Hainfield et al has reviewed application of AuNPs as radiosensitizers that increase local drug dose and at the same time enhance radiation effects [213].…”