In vivo toxicity evaluation of gold-dendrimer composite nanodevices with different surface charges

Abstract

Composite nanodevices (CNDs) are multifunctional nanomaterials with potential uses in cancer imaging and therapy. Poly(amidoamine) dendrimer-based composite nanodevices are important members of this group and consist of an organic dendrimer component and an incorporated inorganic component, in this case, gold. This study addresses the short- (14 days) and long-term (78 days) in vivo toxicity of generation-5 (G5; 5 nm) PAMAM dendrimer-based gold-CNDs (Au-CNDs) with varying surface charges (positive, negative and neutral) in C57BL/6J male mice. Detailed toxicological analyses of (1) body weight changes, (2) serum chemistry and (3) histopathological examination of 22 organs showed no evidence of organ injury or organ function compromise. Zeta potential of Au-CNDs showed significant change from their parent dendrimers upon gold incorporation, making the normally lethal positive surface dendrimer biologically safe. Also homeostatic mechanisms in vivo may compensate/repair toxic effects, something not seen with in vitro assays.

Keywords::

• Composite nanodevice
• in vivo toxicity
• PAMAM dendrimer
• nanoparticle
• biosafety

Acknowledgements

We want to thank Ripen Misri, Nelson Wong and Christine Lum for their assistance in the editing of this manuscript. This study was supported by in part by National Institute of Health (5R01 CA104479) and Department of Defense (W81XWH-07-1-0504) grants to Drs. Khan and Balogh.