Toxicity And Biological Activity Of Several Typical Nanomaterials

This research mainly focuses on the biological effect of nanomaterials such as silver nanoparticles (nanosilver), quantum dots (QDs) and multi-walled carbon nanotubes (MWNTs). It consists of the following three parts:First, the biodistribution of nanosilver in experimental fish was investigated. Nanosilver has been used in chemistry, electronics and medicine. The influence of large amount of nanosilver on ecosystem and environment hasn't been well understood. In this work, we studied the biodistribution of nanosilver in Japanese medaka (oryzias latipes) and Chinese Rare Gudgeon (Gobiocypris rasus) using graphite furnace atomic absorption spectrometry (GFAAS). The results revealed that nanosilver could accumulate in liver, brain and gill in a short time. There was no obvious damage in liver, brain and gill, but potential riskes are available because nanosilver could easily penetrate through the blood-brain barrier (BBB). Nanosilver had no effect on the growth of fish eggs at a dose of 10 ppm. No short-term toxicity was found in this experiment. Further studies are required to determine long-term toxicity of nanosilver.Second, the biological distribution and toxicity of QDs in mice, and the interaction between QDs and protein (BSA) were studied. Due to their excellent photophysical properties, QDs have potential applications as luminescent biological labels and advanced sensors. In vivo exposure to QDs can lead to potential risks, which stems from the metallic component (Cd), the high surface-area-to-volume ratio and small size. In this work, we studied in vivo distribution of QDs in mice using fluorescence spectroscopy method. The results revealed that the majority of the QD dose was in liver and kidney but little uptake in heart, spleen and lung. The largest amounts of QDs in tissues appeared at 2 hours after intravenous dosing. After 6 hours' exposure, liver and kidney were damaged seriously, possibly because of the structure change of QDs in tissues. Interaction between QDs and protein was partially irreversible. QDs could quench the intrinsic fluorescence of protein and induced its secondary structure change, leading to the exposure of hydrophobic group inside the protein to the solvent. This interaction could induce in vivo toxicity of QDs.Third, the interaction of functionalized MWNTs and proteins was studied. Functionalized carbon nanotubes have the potential to be applied in the treatment and diagnosis of diseases. However, their potential effects on biological systems need to be addressed. In this work, we used spectroscopic methods to investigate interactions between functionalized multi-walled carbon nanotubes (f-MWNT) with various proteins. MWNT was chemically modified to produce carboxyl-, Fmoc-tyrosine- and isobutyl-MWNTs. Using Bradford method and HPLC, we first quantified the total protein adsorption ability of each f-MWNT and the specific adsorption of each f-MWNT to each protein. Carboxyl-MWNT showed the strongest protein adsorption ability. The binding of f-MWNT with proteins was also studied by steady state and time resolved fluorescence spectroscopy. Addition of f-MWNT into protein induced quenching of the protein intrinsic fluorescence in the order of carboxyl-MWNT> Fmoc-tyrosine-MWNT>isobutyl-MWNTs>pristine MWNT. Based on CD studies, nanotube/protein binding induced small changes in protein secondary structure in case of carboxyl-MWNT, but less so in other f-MWNTs. F-MWNT could interact with protein molecules through electrostatic, π-π, and hydrophobic interactions. Our results showed that the electrostatic interaction was stronger than other binding forces. Such f-MWNT-protein interactions may trigger partial protein conformational changes and possibly cause the formation of cryptic epitopes that may produce inappropriate cellular responses and result in cellular toxicity.As a whole, this paper firstly studied the ecological toxicity of nanosilver, and found it was nontoxic to experimental fish in short term. Then the in vivo toxicity of QDs and the interaction between QDs and protein were studied. It showed that QDs was extremely toxic to mice and it could irreversibly bind to protein. At last, the interaction of functionalized MWNTs and proteins was studied. It showed that the biological active of MWNTs was relative to the chemical modification of them, and the interaction was selective when different proteins were involved.