title: Pharmacokinetic and toxicological evaluation of multi-functional thiol-6-fluoro-6-deoxy-D-glucose gold nanoparticles in vivo.
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.
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, AB, Canada.
authors.forename: Wilson
authors.initials: W
authors.lastname: Roa
authors.forename: Yeping
authors.initials: Y
authors.lastname: Xiong
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.forename: Kun
authors.initials: K
authors.lastname: Song
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yang
authors.forename: Beihua
authors.initials: B
authors.lastname: Kong
authors.forename: John
authors.initials: J
authors.lastname: Wilson
authors.forename: James Z
authors.initials: JZ
authors.lastname: Xing
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001940:Breast / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006046:Gold / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D013438:Sulfhydryl Compounds; C035308:6-deoxy-6-fluoroglucose; D006046:Gold; D003847:Deoxyglucose