The Time‐Course Effect of Biodistribution and Degradation of Gold Shell Nanoparticles After the Repeated Intravenous Exposure

Abstract Nanomaterials have been developed for various biological applications. In particular, the gold shell nanoparticles (GSNs) featured with the unique core‐shell structure are promising for clinical applications. It is thus imperative to evaluate the long‐term toxicological effects of GSNs. In this study, the histomorphology, biodistribution, and toxicity of GSNs were examined at 1 and 30 days post‐injection to reveal the biological effects over time. Interestingly, we observed the progressive aggregation of GSNs, which subsequently moved to the central venous region as extending the exposure time. The administrated dose of GSNs lower than 5 mg kg −1 in mice shows good biosafety since they can be cleared out gradually. While the administration of GSNs at the dose of 50 mg kg −1 causes accumulation and toxicity to the liver and kidney. We found that the disintegration of GSNs is attributed to the low pH and a high concentration of reactive oxygen species in vivo. Our study reveals the time‐dependent toxicity, organ‐targeted damage, biodistribution, and degradation of GSNs after repeated long‐term exposure in vivo. Our findings will facilitate the rational design of nanoagents and bring new insights into the toxicity of nanoagents for future clinical applications.