Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed.

/pdf/gold-nanoparticles-as-novel-agents-for-cancer-therapy-2c7049xpei.pdf

Gold nanoparticles as novel agents for cancer therapy

Gold nanoparticles for applications in cancer radiotherapy: Mechanisms and recent advancements.

Cancer is the current leading cause of death worldwide, responsible for approximately one quarter of all deaths in the USA and UK. Nanotechnologies provide tremendous opportunities for multimodal, site-specific drug delivery to these disease sites and Au nanoparticles further offer a particularly unique set of physical, chemical and photonic properties with which to do so. This review will highlight some recent advances, by our laboratory and others, in the use of Au nanoparticles for systemic drug delivery to these malignancies and will also provide insights into their rational design, synthesis, physiological properties and clinical/preclinical applications, as well as strategies and challenges toward the clinical implementation of these constructs moving forward.

/pdf/size-matters-gold-nanoparticles-in-targeted-cancer-drug-2r2i7unq1d.pdf

Size matters: gold nanoparticles in targeted cancer drug delivery.

Gold nanoparticles possess a unique combination of properties which allow them to act as highly multifunctional anti-cancer agents (X. H. Huang, P. K. Jain, I. H. El-Sayed and M. A. El-Sayed, Nanomedicine, 2007, 2, 681-693; P. Ghosh, G. Han, M. De, C. K. Kim and V. M. Rotello, Adv. Drug Delivery Rev., 2008, 60, 1307-1315; S. Lal, S. E. Clare and N. J. Halas, Acc. Chem. Res., 2008, 41, 1842-1851; D. A. Giljohann, D. S. Seferos, W. L. Daniel, M. D. Massich, P. C. Patel and C. A. Mirkin, Angew. Chem., Int. Ed., 2010, 49, 3280-3294). Not only can they be used as targeted contrast agents for photothermal cancer therapy, they can serve as scaffolds for increasingly potent cancer drug delivery, as transfection agents for selective gene therapy, and as intrinsic antineoplastic agents. This tutorial review will highlight some of the many forms and recent applications of these gold nanoparticle conjugates by our lab and others, as well as their rational design and physiologic interactions.

/pdf/beating-cancer-in-multiple-ways-using-nanogold-c5btwjaad8.pdf

Beating cancer in multiple ways using nanogold

Inorganic nanoparticles for cancer imaging and therapy.

Glucose-capped gold nanoparticles (Glu-GNPs) have been used to improve cellular targeting and radio-sensitization. In this study, we explored the mechanism of Glu-GNP enhanced radiation sensitivity in radiation-resistant human prostate cancer cells. Cell survival and proliferation were measured using MTT and clonogenic assay. Flow cytometry with staining by propidium iodide (PI) was performed to study the cell cycle changes induced by Glu-GNPs, and western blotting was used to determine the expression of p53 and cyclin proteins that correlated to cell cycle regulation. With 2 Gy of ortho-voltage irradiation, Glu-GNP showed a 1.5-2.0 fold enhancement in growth inhibition when compared to x-rays alone. Comparing the cell cycle change, Glu-GNPs induced acceleration in the G0/G1 phase and accumulation of cells in the G2/M phase at 29.8% versus 18.4% for controls at 24 h. G2/M arrest was accompanied by decreased expression of p53 and cyclin A, and increased expression of cyclin B1 and cyclin E. In conclusion, Glu-GNPs trigger activation of the CDK kinases leading to cell cycle acceleration in the G0/G1 phase and accumulation in the G2/M phase. This activation is accompanied by a striking sensitization to ionizing radiation, which may have clinical implications.

https://iopscience.iop.org/article/10.1088/0957-4484/20/37/375101/pdf

Gold nanoparticle sensitize radiotherapy of prostate cancer cells by regulation of the cell cycle.

We synthesized a novel, multi-functional, radiosensitizing agent by covalently linking 6-fluoro-6-deoxy-d-glucose (6-FDG) to gold nanoparticles (6-FDG–GNPs) via a thiol functional group. We then assessed the bio-distribution and pharmacokinetic properties of 6-FDG–GNPs in vivo using a murine model. At 2 h, following intravenous injection of 6-FDG–GNPs into the murine model, approximately 30% of the 6-FDG–GNPs were distributed to three major organs: the liver, the spleen and the kidney. PEGylation of the 6-FDG–GNPs was found to significantly improve the bio-distribution of 6-FDG–GNPs by avoiding unintentional uptake into these organs, while simultaneously doubling the cellular uptake of GNPs in implanted breast MCF-7 adenocarcinoma. When combined with radiation, PEG–6-FDG–GNPs were found to increase the apoptosis of the MCF-7 breast adenocarinoma cells by radiation both in vitro and in vivo. Pharmacokinetic data indicate that GNPs reach their maximal concentrations at a time window of two to four hours post-injection, during which optimal radiation efficiency can be achieved. PEG–6-FDG–GNPs are thus novel nanoparticles that preferentially accumulate in targeted cancer cells where they act as potent radiosensitizing agents. Future research will aim to substitute the 18F atom into the 6-FDG molecule so that the PEG–6-FDG–GNPs can also function as radiotracers for use in positron emission tomography scanning to aid cancer diagnosis and image guided radiation therapy planning.

https://iopscience.iop.org/article/10.1088/0957-4484/23/37/375101/pdf

Pharmacokinetic and toxicological evaluation of multi-functional thiol-6-fluoro-6-deoxy-d-glucose gold nanoparticles in vivo

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Gold nanoparticle sensitize radiotherapy of prostate cancer cells by regulation of the cell cycle.

Pharmacokinetic and toxicological evaluation of multi-functional thiol-6-fluoro-6-deoxy-d-glucose gold nanoparticles in vivo