Protein corona influences liver accumulation and hepatotoxicity of gold nanorods

•Injected AuNRs were removed from the blood circulation by a heat-stable, opsonin-mediated clearance, mainly by Kupffer cells.•Pre-incubation with mouse serum resulted in the opsonization of AuNRs ex vivo, and enhanced their liver-targeting ability.•The stealth property endowed by the corona of serum albumin helped some AuNRs escape the clearance by Kupffer cells.•AuNRs coated with serum albumin could reach the hepatocytes, thereby possessed a longer retention in the liver.

This work aimed to examine whether the surface coating with serum proteins could influence the in vivo metabolic pattern and toxicity of nanoparticles (NPs). Gold nanorods (AuNRs) were synthesized and employed as a model NPs, and were pre-incubated with mouse serum or mouse serum albumin before intravenous injection. The hepatic uptake and location of AuNRs were examined by ICP-MS and TEM; the hepatotoxicity of AuNRs was evaluated in terms of blood biochemistry, oxidant stress and histopathology. The results showed that AuNRs could be removed from blood circulation by Kupffer cells. Heat stable opsonin proteins played a dominant role in the liver-targeting of AuNRs. Serum albumin corona could confer a certain degree of stealth property to AuNRs, therefore some of them escaped the clearance by Kupffer cells and entered the hepatocytes. It might lead to a long-term retention of AuNRs in the liver. The findings may have important implications for the understanding of the in vivo behavior of NPs as well as the design of NPs-based drug delivery system.

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