Biodistribution and acute toxicity of naked gold nanoparticles in a rabbit hepatic tumor model

Abstract

There is a paucity of data regarding the safety of administering solid gold nanoparticles (AuNPs) in large animal tumor models. We assessed the acute toxicity and biodistribution of 5 nm and 25 nm solid AuNPs in New Zealand White rabbits (n = 6 in each) with implanted liver Vx2 tumors 24 h after intravenous injection. Gold concentration was determined by inductively coupled plasma atomic emission spectrometry (ICP) and imaged with transmission electron microscopy (TEM). There was no clinico-pathologic evidence of renal, hepatic, pulmonary, or other organ dysfunction. After 25 nm AuNP administration, the concentration of white blood cells increased after treatment (p = 0.001). Most other blood studies were unchanged. AuNPs were distributed to the spleen, liver, and Vx2 tumors, but not to other tissues. The urinary excretion of AuNPs was bimodal as measured by ICP. 25 nm AuNPs were more evenly distributed throughout tissues and may be better tools for medical therapy.

Keywords::

• Gold nanoparticle
• tumor model
• biodistribution
• acute toxicity

Acknowledgements

The authors would like to acknowledge the staff and animal care technologists of the Department of Veterinary Medicine and Surgery, specifically Maurice J Dufilho, IV, and Darla Y. Stange for assistance with necropsy and Vx2 cell culture. Kenneth Dunner, Jr., of The High Resolution Electron Microscopy Facility at The University of Texas M.D. Anderson Cancer Center provided valuable assistance with TEM imagining. The authors would also like to thank Kristine Ash and Yolanda Brittain for administrative support.

Author contributions

ESG & SAC designed the experiments and wrote the manuscript. ESG, CZ, ANH, AB, and CST performed the experiments. ESG and ANH analyzed the data. All authors were involved in editing the final manuscript and approved its final form.

Funding sources

This work was partially funded from the NIH (U54CA143837 and Core Grant CA16672) and an unrestricted research grant from the Kanzius Foundation (SAC, Erie, PA). In addition, ESG is an NIH T32 research fellow (T32 CA09599).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.