No abstract

It is generally known that gold nanoparticles are localised in the cytoplasm and, if synthesised in small sizes or functionalized with specific proteins, they enter the cell nucleus. However, there is no report emphasising the importance of surface functionalization in their accumulation in the nucleolus. Here, for the first time in the literature, it is proposed that functionalization of gold nanoparticles with a thin layer of polyethyleneimine (PEI) spearheads them to the nucleolus of hard-to-transfect post-mitotic dorsal root ganglion neurones in a size-independent manner. As a potential for theranostic applications, it was found that functionalization with a thin layer of PEI affected the emission signal intensity of gold nanoparticles so that the cellular biodistribution of nanoparticles was visualised clearly under both confocal and two-photon microscopes.

With the development of gold nanorods (AuNRs) for a number of biomedical applications, understanding their various biological effects has become important. Surface functionalization of AuNRs is attracting increasing attention with regard to toxicity, cellular uptake, localization, therapeutic potential, and biodistribution. The aim of the study is to synthesis of stable AuNRs functionalized with polyethylenimine (PEI) and polyethylene glycol (PEG), multiparametric investigation of their cellular effects on the dorsal root ganglion (DRG) primary sensory neurones, evaluation of the in vitro/in vivo biodistribution, and toxicity. PEI and PEG surface coatings increased both biocompatibility and biodistribution of the AuNRs. With the near‐infrared laser of the two‐photon microscope, very strong radiations are taken from the nucleolus parts of the neurones particularly and these localizations of the AuNRs‐PEI are confirmed by the transmission electron microscope images. Inductively coupled plasma mass spectrometry analysis shows the presence of AuNRs in liver, spleen, kidney, heart, blood, and brain within a 30 day period. It is observed that the surface coatings of the AuNRs significantly increase the biodistribution and biocompatibility. The surface functionalization, stability, and biocompatibility of the AuNRs are very important parameters for the potential nanotheranostic applications of AuNRs in the next studies.

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.