Cellular Toxicological Effects Of Organic Ultraviolet Filtering Materials And Construction Of Cyclodextrin Inclusion Compounds

Ultraviolet filtering materials(UVAs)are used as new mechanical materials to protect against UV radiation,and thus prevent degradation of the mechanical properties of machine components.Current research on the properties of UVAs is mainly focused on physicochemical properties,while the research on biological properties of UVAs is still at a preliminary stage,especially the effects and mechanisms of UVAs on human health effects are still unclear.Most UVAs are insoluble in water and have poor biocompatibility,limiting their application.Cyclodextrins(CDs)can encapsulate substances to improve biocompatibility and water solubility,expanding the field of application.The study is based on the combination of chemical and interdisciplinary approaches such as cell biology and molecular biology to select the cellular biological properties and molecular mechanisms of UVAs.The construction of watersoluble UVAs was carried out through host-guest interactions and the comprehensive study of their cellular biological properties was undertaken.The details of the study are as follows:1.The cellular cytotoxic effects of benzophenone-1(BP-1),benzophenone-3(BP-3),isoamyl 4-methoxycinnamate(IMC)and 2-Ethylhexyl 4-methoxycinnamate(OMC),four UVAs were initially assessed using the CCK-8 method and morphological observations.Benzophenones(BPs)and cinnamates UVAs(CUVAs)inhibited the growth and multiplication of human hepatoma SMMC-7721 cells and reduced cell density.BPs and CUVAs caused cell nuclear morphology to be crinkled,agglutinated or fragmented,early apoptosis of cells and decreased mitochondrial membrane potential(MMP).2.The toxicological mechanisms of UVAs were studied based on the level of oxidative stress.The level of reactive oxygen species(ROS)increased when the cells were exposed to BPs and CUVAs.Antioxidant enzyme activity reduced,such as superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px).Malondialdehyde(MDA)levels increased,and lactate dehydrogenase(LDH)enzyme activities increased.It indicated that the intracellular oxidative stress system was disturbed.The molecular docking results showed that BPs and CUVAs could form more stable binding to the main enzymatic proteins of the oxidative stress system in the following order: CAT>LDH-A>GPX1>SOD1.A comprehensive macro-micro analysis of UVAs disrupted the oxidative stress system and leads to apoptosis.3.The toxicological mechanisms of UVAs were studied based on the level of gene expression.The results showed that Bax m RNA and Caspase-3 m RNA were up-regulated,and Bcl-2 m RNA was downregulated after the intervention of BPs and CUVAs.UVAs could participate in the apoptotic process by regulating the expression of Bax and Bcl-2 m RNA,and the process of apoptosis was associated with the release of Caspase-3 m RNA.4.The toxicological mechanisms of UVAs were studied based on the level of protein expression.The results showed that BPs and CUVAs increased the expression of the pro-apoptotic protein Bax and decreased the expression of the anti-apoptotic protein Bcl-2.It can be seen that UVAs can interfere with intracellular protein synthesis and secretion processes.The structure and function of the cells to maintain normal physiological activities were damaged.5.The new UVAs were constructed using the saturated solution method and solid phase synthesis method using IMC and sulfobutyl-β-cyclodextrin(SBE-β-CD)as the system,and the toxicological effects and molecular mechanisms of the new UVAs were investigated.The phase solubility method showed that IMC-SBE-β-CD was most stable at the temperature of 30°C,and the package junction ratio of IMC to SBE-β-CD was 1:1.FT-IR and XRD showed that the characteristic and diffraction peaks of IMC were masked in IMC-SBE-β-CD and new characteristic and diffraction peaks appeared,indicating the generation of IMC-SBE-β-CD inclusion complexes.Toxicological studies showed that IMC-SBE-β-CD promoted cell growth and reproduction,with an increase in the number of cells within the field of view.The nuclei showed a dark blue distribution and did not cause any change in the MMP.The intracellular ROS level was reduced,enzyme activities of SOD,CAT and GSH-Px were increased,while LDH enzyme activity and MDA content were reduced.It showed that the cells did not show oxidative stress disorder.Bax m RNA and Caspase-3 m RNA were down-regulated,and Bcl-2 m RNA was up-regulated after IMCSBE-β-CD intervention.The apoptotic protein expression trends were consistent with the gene expression trends.In summary,this thesis focused on the biological properties of UVAs,systematically investigated the toxicological effects and molecular mechanisms of UVAs,and illustrated that the water solubility and biocompatibility of UVAs could be improved after encapsulation of UVAs by cyclodextrins.The relevant results deepen the understanding of the biological properties of UVAs and provide a theoretical and experimental basis for the construction and rational application of CDs-encapsulated UVAs.