Abstract
Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations. Chemotoxicity was prevented by co-administration of N-acetyl cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK. In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at low concentrations is a novel discovery that holds great promise in developing low-cost cancer nanotherapeutics.
Highlights
Radiotherapy is currently used in around half of all cancer treatments
The core size of the synthesised and citrate AuNPs was determined by Transmission electron microscopy (TEM) analysis, and demonstrated mean values between 1.7–2.4 nm, regardless of the ligands added during AuNP synthesis (Table 1, TEM images and histograms are shown in S1 Fig)
1H-NMR analysis of three different αGal:PEG-amine AuNPs revealed a slight preference for PEG-amine over αGal for attachment to AuNPs during synthesis
Summary
Radiotherapy is currently used in around half of all cancer treatments. generally effective, it is damaging to surrounding healthy tissues and needs to be improved by better targeting of cancer cells. One promising approach is to use nanoparticles composed of high atomic number elements, such as gold, hafnium, gadolinium, platinum or iron, which have large X-ray photon capture cross-sections, and can locally increase the energy deposition near the nanoparticle through secondary electron emission from the nanoparticles [1,2,3]. Because of their biocompatibility and amenability to surface modification for tumour targeting, gold nanoparticles (AuNPs) have predominantly been used for tumour radiosensitisation studies [4,5,6]. AuNP radiosensitisation with external beam sources is more effective when
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