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Interactions between Titanium Dioxide Nanoparticles (NPs) and mucin

Titanium dioxide nanoparticles (TiO2 NPs) are widely used in many food, consumer, and industrial products. However, little is known about the overall effects of TiO2 NPs on the environment or human health. In order to elucidate the fate, transformation, transport, and toxicological impact of TiO2 NPs, a better understanding is needed of how the physicochemical properties of TiO2 NPs (e.g. size, charge, curvature, hydrophobicity, and surface functionality) interact with their microenvironments (e.g. pH, temperature, bile acids, microbiome, enzymes, surface-active components, and biopolymers). Living organisms including humans have a natural mechanism to protect themselves from physical, biological, and chemical perils by generating mucin—the main gel-forming polymers of mucus and consists of core protein domains and densely O-linked oligosaccharide chains. However, there is a very limited study even no study examining the interaction between TiO2 NPs and mucin comprehensively. This thesis was divided into three parts: first, a literature review focusing on the major routes of TiO2 NPs entered the environment and human body, and the mechanistic interactions of biomolecules on the surface of TiO2 NPs; the second part, the effect of TiO2 NPs-mucin interaction on the alteration of physicochemical properties of TiO2 NPs and mucin during the formation of biomolecular corona (BMC), aggregation and accumulation of TiO2 NPs in water; the last part, the effect of phosphate-buffered saline (PBS) and pH to the change of surface charge, the formation of BMC, and hetero aggregation. There were several major pathways of TiO2 NPs entered the environment and the human system. TiO2 NPs interacted with the human system via the respiratory system, skin, and gastrointestinal (GI) tract. Interaction between TiO2 NPs and mucin might be induced by polyvalent binding as evidenced by three or more ligands (TiO2 NPs) that were likely to interact with one molecule receptor (mucin). TiO2 NPs-mucin interaction (at a mass ratio of TiO2 NPs and mucin= 0.25) was likely to cause the massive hetero aggregation since evidenced by the increase of size, the hypochromic effect and redshift of UV-Vis spectra, and the appearance of spectral peaks of TiO2 NPs and mucin by the surface-enhanced Raman Spectroscopy (SERS). The formation of unstable hetero aggregation in PBS required a higher concentration of TiO2 NPs than in DIW. In deionized water (DIW), cationic BMC was potentially developed in acidic conditions; while in PBS there was, no cationic BMC formed. It might be caused by the effect of buffers and pH on physicochemical properties of TiO2 NPs, particularly the surface charge. Surface charges of TiO2 NPs in DIW were changed from positive to negative with the increase of pH, while surface charges of TiO2 NPs in PBS were all negative in various pH. Albeit both TiO2 NPs and mucin in PBS had a negative surface charge, SERS exhibited that TiO2 NPs-mucin interaction still occurred. In conclusion, the interaction between TiO2 NPs and mucin is potentially polyvalent binding and thereby induces irreversible hetero aggregation through various interactions. Further studies to know the types of interaction, reaction products, and possible consequences are required.
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