title: The biodistribution and pharmacokinetic evaluation of choline-bound gold nanoparticles in a human prostate tumor xenograft model.
abstract: OBJECTIVE
  Gold nanoparticles (GNPs) have attracted significant attention in the treatment of cancer due to their potential as novel radiation enhancers, particularly when functionalized with various targeting ligands. The aim of this study was to assess the biodistribution and pharmacokinetic characteristics of a novel choline-bound GNP (choline-GNP) stabilized with polyethelenimine (PEI).
  
  
  METHODS
  Choline bound to 27 nm diameter GNPs was characterized using transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Toxicity of choline-GNPs was examined on DU-145 prostate cancer cells using an MTT assay. Using balb/c mice bearing flank DU-145 prostate tumors, choline-GNPs bio-distribution was measured using inductively coupled mass spectroscopy (ICP-MS). Blood, heart, lung, liver, spleen, brain, kidney and tumor gold content were examined at multiple time points over a 24-hour period after tail vein injection.
  
  
  RESULTS
  An MTT assay using DU-145 prostate cancer cells yielded a 95% cell viability 72 hours after choline-GNP administration. The tumor GNP area under the concentration-time curve during the first 4 hours (AUC0-4) was 2.2 µg/ml h, representing 13% of the circulating blood GNP concentration over the same time period. The maximum intra-tumor GNP concentration observed was 1.4% of the injected dose per gram of tumor tissue (%ID/g) one hour post injection.
  
  
  CONCLUSIONS
  GNPs functionalized with choline demonstrates a viable future nanoparticle platform with increased intra-tumor uptake as compared to unconjugated GNPs. Decreased intra-hepatic accumulation appears to be the reason for the improved systemic bioavailability. The next logical translational investigation will incorporate external beam radiation with the observed maximum intra-tumor uptake.
authors.affiliation: Division of General Surgery, Department of Surgery, University of Alberta Hospital, Edmonton, Alberta, Canada.
authors.forename: Rene
authors.initials: R
authors.lastname: Razzak
authors.forename: Joe
authors.initials: J
authors.lastname: Zhou
authors.forename: XiaoHong
authors.initials: X
authors.lastname: Yang
authors.forename: Nadim
authors.initials: N
authors.lastname: Pervez
authors.forename: Eric Lr
authors.initials: EL
authors.lastname: Bédard
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Moore
authors.forename: Andrew
authors.initials: A
authors.lastname: Shaw
authors.forename: John
authors.initials: J
authors.lastname: Amanie
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Roa
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002794:Choline / Q000378:metabolism*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D051379:Mice; D056951:Photoelectron Spectroscopy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D006046:Gold; D002794:Choline