Effects of surface charges of gold nanoclusters on long-term in vivo biodistribution, toxicity, and cancer radiation therapy

Abstract

Gold nanoclusters (Au NCs) have exhibited great advantages in medical diagnostics and therapies due to their efficient renal clearance and high tumor uptake. The in vivo effects of the surface chemistry of Au NCs are important for the development of both nanobiological interfaces and potential clinical contrast reagents, but these properties are yet to be fully investigated. In this study, we prepared glutathione-protected Au NCs of a similar hydrodynamic size but with three different surface charges: positive, negative, and neutral. Their in vivo biodistribution, excretion, and toxicity were investigated over a 90-day period, and tumor uptake and potential application to radiation therapy were also evaluated. The results showed that the surface charge greatly influenced pharmacokinetics, particularly renal excretion and accumulation in kidney, liver, spleen, and testis. Negatively charged Au NCs displayed lower excretion and increased tumor uptake, indicating a potential for NC-based therapeutics, whereas positively charged clusters caused transient side effects on the peripheral blood system.

Keywords:

• gold clusters
• in vivo toxicity
• long-term
• cancer therapy

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Nos 81471786, 11304220, 81000668), Natural Science Foundation of Tianjin (Nos 13JCQNJC13500, 14JCYBJC26700), and the Subject Development Foundation of Institute of Radiation Medicine, CAMS (Nos SF1601, SF1503).

Disclosure

The authors report no conflicts of interest in this work.