Biodistribution of TNF-alpha-coated gold nanoparticles in an in vivo model system.
OBJECTIVE
In this study, we describe the biodistribution of CYT-6091, a colloidal gold (Au)-based nanomedicine that targets the delivery of TNF-alpha to solid tumors.


METHODS
A single intravenous injection of CYT-6091 coated with 5 microg TNF-alpha was given to human prostate tumor-bearing or naive (without tumor) nude mice. Tissues were harvested and analyzed at specific time points for Au nanoparticles by atomic emission spectroscopy and TNF-alpha by ELISA.


RESULTS
The two constituents of CYT-6091, TNF-alpha and Au, exhibited different behavior in blood, with TNF-alpha showing a faster decay than the Au nanoparticles. Between 0 and 4 h after injection, TNF-alpha showed a preferential accumulation in the tumor. Au was observed to accumulate preferentially in the liver between 4 and 12 h, and showed some clearance over time (4 months).


CONCLUSIONS
These data suggest that CYT-6091 delivers TNF-alpha preferentially to the tumor and that upon TNF-alpha degradation, the liver takes up Au, which is cleared slowly over time.
Goel
Raghav
R
Department of Biomedical Engineering, University of Minnesota, MN, USA.
Shah
Neha
N
Visaria
Rachana
R
Paciotti
Giulio F
GF
Bischof
John C
JC
D000818:Animals; D017979:Gold Colloid / Q000737:chemistry*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000648:ultrastructure; D013154:Spleen / Q000378:metabolism / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000627:therapeutic use
D017979:Gold Colloid; D014409:Tumor Necrosis Factor-alpha