Uncovering the Fate and Risks of Intravenously injected Prussian Blue Nanoparticles in mice by an Integrated Methodology of Toxicology, Pharmacokinetics, Proteomics and Metabolomics

Abstract Background: Nanomaterials (NMs) have been widely explored in the biomedical field such as imaging diagnosis, drug delivery and novel therapeutics. However, increasing studies have revealed the potential bio-toxicities of NMs. For instance, carbon nanotube (CNT) has been added to the international dangerous goods list as a 2B carcinogen due to the potential carcinogenicity and reproductive toxicity after long-term exposure. Therefore, the in-depth understanding of the toxicity of candidate medical NMs is quite essential and very instructive for their further medical applications. Prussian blue (PB) nanoparticles (NPs) have been intensively investigated for medical applications, while the in-depth toxicological investigation of PB NPs has not been implemented to date. Results: In this study, the fate and potential risks of intravenous injected PB NPs were systematically investigated in mice by an integrated methodology of toxicology, pharmacokinetics, proteomics and metabolomics. General toxicological studies demonstrated that intravenous injection of PB NPs at 5 or 10 mg/kg could not induce obvious toxicity to mice, while mice treated with a relatively high dose of PB NPs at 20 mg/kg exhibited loss of appetite and weight decreasing in the first two days post-injection. Pharmacokinetic studies revealed that the intravenously administered PB NPs underwent a fast clearance from blood and highly accumulated in the livers and lungs, and finally cleared from mice tissues. Conclusions: The integrated investigation demonstrated that slight inflammatory responses and intracellular oxidative stress were induced in the liver and lungs of mice during the exposure to PB NPs. Collectively, our experimental data implies that the high dose of PB NPs may cause potential risks to liver and lungs, indicating that people should pay more attention to these two critical organs if taking PB NPs as therapeutic.