Gold nanoparticles are promising candidates as vehicles for drug delivery systems and could be developed into effective anticancer treatments. However, concerns about their safety need to be identified, addressed, and satisfactorily answered. Although gold nanoparticles are considered biocompatible and nontoxic, most of the toxicology evidence originates from in vitro studies, which may not reflect the responses in complex living organisms.

In this work, the consequences of the long-term exposure to AuNPs on the structure and function of three vital organs – liver, spleen, and kidneys have been studied to help identify the key features of AuNPs accumulation in the tissues that might lead to their toxicity. The long-term accumulation of BSA-AuNPs in the liver and spleen did not affect the function of the two organs. However, detected changes in the structure of these organs including increased infiltration of macrophages and increased fibronectin level suggested toxic response associated with the chronic exposure to AuNPs. Whether such changes are transient and would resolve over the time or they represent an initial stage of a progressive inflammatory process need to be confirmed further. Increased fibronectin in renal glomeruli associated with albuminuria, despite negligible BSA-AuNPs accumulation in the kidneys, underline the complex response of the organism to the long-term nanoparticle deposition, which should be considered by AuNPs toxicological profiling. It would be interesting to find out whether such early signs of a kidney injury could be avoided through the use of pharmaceuticals.

Our data suggest, that although AuNPs belong to the safest nanomaterial platforms nowadays, due to their slow tissue elimination leading to long-term accumulation in the biological systems, they may induce toxic responses in the vital organs, and so understanding of their long-term biological impact is important to consider their potential therapeutic applications.

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