13 research outputs found
Cancer-selective, single agent chemoradiosensitising gold nanoparticles
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
TEM images of A,B) HSC-3 and C,D) HaCaT cells incubated for 3 h with 10 μg/ml 0:100 αGal:PEG-amine AuNPs.
<p>Boxed area in A is shown magnified in B. Scale bars A,C are 500 nm; B,D are 100 nm.</p
Normalised survival fractions of (A,C) HSC-3 and (B,D) HaCaT cells following exposure to αGal:PEG-amine AuNPs at their HSC-3 IC50 concentrations, followed by different doses of (A,B) 220 kV X-rays or (C.D) 6 MV X-rays.
<p>Data are presented as the mean survival fraction ±SEM. A linear-quadratic curve was fitted to each data series.</p
Clonogenic assay dose-response of adherent MCF-7 and MCF-10 cells exposed for 3 h to different concentrations of 50:50 or 0:100 αGal:PEG-amine AuNPs.
<p>The graphs represent the percentage of cell colonies compared to the no-nanoparticle control ±SEM.</p
Clonogenic assay dose-response of different ratios of αGal:PEG-amine AuNPs, citrate-capped AuNPs, αGal only, or PEG-amine only, loaded for 3 h on adherent cells.
<p>a) HSC-3 cells, b) HaCaT cells. The graphs represent the percentage of cell colonies compared to the no-nanoparticle control ±SEM.</p
TEM images of A,B) HSC-3 and C,D) HaCaT cells incubated for 3 h with 10 μg/ml 50:50 αGal:PEG-amine AuNPs.
<p>Boxed areas in A and C are magnified in B and D, respectively. Arrows indicate AuNPs within cytoplasm; n, nucleus; m, mitochondrion; scale bars A,C are 500 nm; B,D are 100 nm.</p
Clonogenic assay of (A,B) MCF-7 and (C,D) MCF-10 cells following exposure to αGal:PEG-amine AuNPs at their MCF-7 IC50 concentrations, then different doses of A,C) 220 kV X-rays or B,D) 6 MV X-rays.
<p>Clonogenic assay of (A,B) MCF-7 and (C,D) MCF-10 cells following exposure to αGal:PEG-amine AuNPs at their MCF-7 IC50 concentrations, then different doses of A,C) 220 kV X-rays or B,D) 6 MV X-rays.</p
Sensitivity Enhancement Ratios and Dose Enhancement Factors calculated for breast cells.
<p>Sensitivity Enhancement Ratios and Dose Enhancement Factors calculated for breast cells.</p
Clonogenic assay of HSC-3 cells, demonstrating a partial rescue of 50:50 αGal:PEG-amine AuNP-induced cell death by 50 μM Z-VAD-FMK caspase inhibitor.
<p>10 μM Antimycin A was used as an apoptosis positive control. For each condition, n = 3 and data are presented ±SEM. * Denotes a significant difference (P<0.05 ANOVA, Tukey multiple comparisons post-test).</p