1. Pharmacokinetic and toxicological evaluation of multi-functional thiol-6-fluoro-6-deoxy-D-glucose gold nanoparticles in vivo.
- Author
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Roa W, Xiong Y, Chen J, Yang X, Song K, Yang X, Kong B, Wilson J, and Xing JZ
- Subjects
- Adenocarcinoma pathology, Adenocarcinoma radiotherapy, Animals, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacokinetics, Breast drug effects, Breast pathology, Breast radiation effects, Breast Neoplasms pathology, Breast Neoplasms radiotherapy, Cell Line, Tumor, Deoxyglucose chemistry, Deoxyglucose pharmacokinetics, Deoxyglucose therapeutic use, Female, Gold chemistry, Gold pharmacokinetics, Mice, Nanoparticles chemistry, Radiation-Sensitizing Agents chemistry, Radiation-Sensitizing Agents pharmacokinetics, Radiation-Sensitizing Agents therapeutic use, Sulfhydryl Compounds chemistry, Adenocarcinoma drug therapy, Antineoplastic Agents therapeutic use, Breast Neoplasms drug therapy, Deoxyglucose analogs & derivatives, Gold therapeutic use, Nanoparticles therapeutic use
- Abstract
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 (18)F 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.
- Published
- 2012
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