  Ultrasmall gold nanoclusters show great potential in biomedical applications.
Long term biodistribution, retention, toxicity, and pharmacokinetics profiles
are prerequisites in their potential clinical applications. Here we
systematically investigated the biodistribution, clearance, and toxicity of one
widely used Au NC species glutathione protected Au NCs or GSH Au NCs, over a
relatively long period of 90 days in mice. We observed that most of the Au NCs
were cleared at 30 days post injection with a major accumulation in liver and
kidney. However, it is surprising that an abnormal increase of Au amount in the
heart, liver, spleen, lung, and testis was observed at 60 and 90 days,
indicating that the injected Au NCs formed a V shaped time dependent
distribution profile in various organs. Further investigations revealed that Au
NCs were steadily accumulating in the muscle in the first 30 days p.i., and the
as stored Au NCs gradually released into blood in 30 to 90 days, which induced
a redistribution and reaccumulation of Au NCs in all blood rich organs. Further
hematology and biochemistry studies showed that the reaccumulation of Au NCs
still caused some liver toxicity at 30 days p.i. The muscle storage and
subsequent release may give rise to the potential accumulation and toxicity
risk of functional nanomaterials over long periods of time.

Biological Physics