Histological changes in mice tissues induced by gold nanoparticles with different surface coatings and sizes

Abstract

Aim: Gold nanoparticles (AuNPs) have many biomedical applications due to their unique properties (e.g., chemical stability, optical properties, biocompatibility, easy synthesizability, and multiple functionalizations). This study aimed to synthesize two highly monodispersed and stable AuNPs of different sizes (AuNP20 and AuNP50), modified with polyethyleneimine (PEI) and polyethylene glycol (PEG), and systematically investigate their toxicological effects on histological changes in the organs of BALB/c mice. Methods: AuNPs (AuNP20 and AuNP50) were synthesized, and their surfaces were coated with PEI and PEG. All necessary characterizations were performed. After the application of two different doses of intravenous injections (IV) of the AuNPs (0.5 and 5 mg Au/kg), their toxicological effects and histological changes in the various mice organs (e.g., liver, spleen, kidney, brain) were evaluated with multiple parameters 48 h post injection. Fourteen days after a single high dose (5 mg Au/kg) IV injection of AuNPs, transmission electron microscopy (TEM) analysis was performed to reveal their ultrastructural effects in the liver of the mice. Results: Stable and highly monodispersed AuNPs were synthesized successfully. Since the liver is the most critical organ in nanotoxicological evaluations, changes in the parameters of AuNPs were shown to have remarkable effects. Although there were no differences in the impact caused between the two AuNPs sizes, the microstructure of the liver tissue treated with AuNP nanoparticles with PEI or PEG coatings was similar to that observed in the control group. Microstructural histological changes in the other organs (e.g., brain, kidney, and spleen) were relatively less than those found in the liver. The PEI and PEG surface coatings generally increased the biocompatibility of the AuNPs. According to the TEM analysis data, apparent cellular changes were observed after a long exposure period in the AuNP groups without an additional surface coating. Although slight cellular alterations were observed in the AuNP groups coated with PEG and PEI, the morphology of the hepatocyte cells was generally healthy. Conclusion: The surface coating of the AuNPs was a more decisive parameter than the size of the nanoparticles in terms of in vivo histological toxicity. The stability, biocompatibility, and surface coating of the AuNPs were critical parameters for potential nanoteranostic applications.