Blood Clearance and Tissue Distribution of PEGylated and Non-PEGylated Gold Nanorods After Intravenous Administration in Rats

Abstract

Aims: To develop and determine the safety of gold nanorods, whose aspect ratios can be tuned to obtain plasmon peaks between 650 and 850 nm, as contrast enhancing agents for diagnostic and therapeutic applications. Materials & methods: In this study we compared the blood clearance and tissue distribution of cetyl trimethyl ammonium bromide (CTAB)-capped and polyethylene glycol (PEG)-coated gold nanorods after intravenous injection in the tail vein of rats. The gold content in blood and various organs was measured quantitatively with inductively coupled plasma mass spectrometry. Results & discussion: The CTAB-capped gold nanorods were almost immediately (<15 min) cleared from the blood circulation whereas the PEGylation of gold nanorods resulted in a prolonged blood circulation with a half-life time of 19 h and more wide spread tissue distribution. While for the CTAB-capped gold nanorods the tissue distribution was limited to liver, spleen and lung, the PEGylated gold nanorods also distributed to kidney, heart, thymus, brain and testes. PEGylation of the gold nanorods resulted in the spleen being the organ with the highest exposure, whereas for the non-PEGylated CTAB-capped gold nanorods the liver was the organ with the highest exposure, per gram of organ. Conclusion: The PEGylation of gold nanorods resulted in a prolongation of the blood clearance and the highest organ exposure in the spleen. In view of the time frame (up to 48 h) of the observed presence in blood circulation, PEGylated gold nanorods can be considered to be promising candidates for therapeutic and diagnostic imaging purposes.

Keywords::

• blood clearance
• gold
• nanorods
• systemic administration
• tissue distribution

Financial & competing interests disclosure

This work was funded through the thrust area program NIMTIK of the MIRA Institute (formerly BMTI) of University of Twente, through the PRESMITT project (IPD067771) of the SenterNovem program IOP Photonic Devices, and by the Nederlandse Wetenschappelijke Organisatie (NWO) and Stichting Technische Wetenschappen (STW) through project TTF 6527. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors would like to acknowledge Ron Vlug, Hans Strootman, Liset de la Fonteyne, Nick van Oyen (RIVM), and Amanda Troost–De Jong and Jeannette Smulders (MiPlaza), and Wilma Petersen (MIRA-UT) for their excellent technical support during the study. The authors would also like to acknowledge Jan Van Eijkeren (RIVM) for the mathematical modeling of the data.

Additional information

Funding

This work was funded through the thrust area program NIMTIK of the MIRA Institute (formerly BMTI) of University of Twente, through the PRESMITT project (IPD067771) of the SenterNovem program IOP Photonic Devices, and by the Nederlandse Wetenschappelijke Organisatie (NWO) and Stichting Technische Wetenschappen (STW) through project TTF 6527. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.