| Summary: | 碩士 === 國立清華大學 === 生醫工程與環境科學系 === 98 === While particles reach nanoscale, specific properties of nanoparticles (NPs) may cause more hazard potential to health and environment. Among these common metal oxides NPs, the toxicity of CuO NP is highest. Some studies had reported that after pinocytosing CuO NPs, cells showed specific lethality because of reactive oxygen species (ROS) induced by NPs and some still unknown mechanisms from NPs surface. Furthermore, oxidative stress inducing from ROS and Cu2+ released from CuO NPs would cause DNA oxidative damage.
In this study, (2E, 4E)-5-(4-hydroxyphenyl) penta-2,4-dienoic acid (HPPDA), with conjugated phenols for ROS scavenging and carboxyl group for chemisorption on suface of CuO particles, was designed and synthesized. For scavenging intracellular ROS induced by CuO NPs, decreasing active surface of NPs contact with organisms, and lowering Cu2+ released from surface of particles, we modified CuO particles by coating HPPDA antioxidants to reduce nanotoxicity of CuO and increase environmentally friendly.HPPDA and L-ascorbic acid (a general antioxidant) exposed respectively to human lung carcinoma epithelial cell lines (A549) were study to compare the cytotoxicity through cell lethality and pre-inflammation response. Experimentally, HPPDA shows much more cell tolerance. In addition, the H2O2 scavenging capability of HPPDA is better than ascorbic acid. Thus, it is feasible to reduce cytotoxicity of CuO NPs by modification of HPPDA. HPPDA can be partial ionized its carboxyl group to form self-assembled monolayer (SAM) on the surface of CuO NPs under neutral or weak acidic situation, which was called functional CuO particles (fCuO). The results of cell lethality, stimulation of interleukin-8 secretion, production of intracellular ROS, cell aging and oxidative DNA damage, indicate that the cytotoxicity of fCuO is much lower than of naked CuO. Thus, in the after-treatment of NPs, HPPDA can be the suitable ligands for NPs modification to reduce their nanotoxicity. In addition, comparison of CuO NPs modified by different ligands: oleic acid, L-ascorbic acid and HPPDA (all of them are with carboxyl group but different in antioxidative capability) shows different toxicity in cell lethality. It also indicates that the capability of ligand for reducing nanotoxicity is based on not only decreasing active surface of NPs to contact directly with organisms by modification but the antioxidative capability of ligand itself.
Furthermore, due to outstanding antioxidative capability, very low cytotoxicity and possession of carboxyl group which can modify NPs directly or link other specific groups, HPPDA may be the framework combined with non-toxic or magnetic biomaterials applied for anti-aging in the future.
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