Open AccessThe biodistribution and pharmacokinetic evaluation of choline-bound gold nanoparticles in a human prostate tumor xenograft model
Author(s) -
Rene Razzak,
Joe Q. Zhou,
Xiaohong Yang,
N. Pervez,
Eric L.R. Bédard,
Ronald B. Moore,
Andrew Shaw,
John Amanie,
Wilson Roa
Publication year - 2013
Publication title -
clinical and investigative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.391
H-Index - 47
eISSN - 1488-2353
pISSN - 0147-958X
DOI - 10.25011/cim.v36i3.19724
Subject(s) - biodistribution , choline , chemistry , pharmacokinetics , prostate cancer , colloidal gold , prostate , cancer research , cancer , pharmacology , nanoparticle , medicine , biochemistry , in vitro , materials science , nanotechnology
Purpose: 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.