Storage of Gold Nanoclusters in Muscle Leads to their Biphasic in Vivo Clearance

TL;DR

This study reveals that gold nanoclusters stored in muscle can be released over time, leading to a biphasic clearance pattern and potential long-term toxicity, which is critical for biomedical applications.

Contribution

It provides the first detailed long-term in vivo biodistribution and clearance profile of gold nanoclusters, highlighting muscle as a storage site and revealing biphasic clearance behavior.

Findings

Most Au NCs cleared at 30 days post injection

Au NCs stored in muscle and released over 60-90 days

Reaccumulation caused liver toxicity at 30 days

Abstract

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.