水溶性富勒烯衍生物的合成及抗肿瘤活性研究
发布时间：2019-01-01 19:34
【摘要】：由于C_(60)独特的化学和物理特性,富勒烯及其衍生物的生物活性近年来引起了人们的注意。本论文利用高分子化学、有机化学和生物学的方法对富勒烯衍生物的生物活性这一交叉课题进行了研究。通过MTT 等方法,系统地研究了水溶性富勒烯衍生物的结构与其光诱导的癌细胞毒性功能的关系,并较深入地研究了水溶性富勒烯衍生物光诱导的癌细胞毒性的作用机理。 采用高分子的自由基聚合及分子设计的方法,合成了三种水溶性富勒烯共聚物,即富勒烯-乙烯基吡咯烷酮共聚物,富勒烯-马来酸酐共聚物,富勒烯-丙烯酰胺共聚物。采用有机化学的方法合成了三种水溶性富勒烯衍生物,即富勒烯-赖氨酸衍生物,富勒烯-甘氨酸衍生物,富勒烯-天门冬氨酸衍生物。它们为首次制备。这六个富勒烯衍生物均能很好的溶解在水中。 首次研究了六个水溶性富勒烯衍生物的反应机理及反应条件。并采用凝胶渗透色谱GPC、紫外光谱UV、红外光谱FTIR、核磁共振1HNMR 等分析方法对它们进行了结构表征。利用透射电镜分析发现富勒烯衍生物水溶液的TEM 形貌均为理想的球形,其数均粒径均小于50nm,与之相比,相应均聚物水溶液的TEM 形貌为无定形状。 为验证水溶液富勒烯衍生物对活体肿瘤的光动力学损伤作用,我们首次进行了动物体内实验:富勒烯-马来酸酐衍生物对裸鼠的骨肉瘤的光动力学杀伤作用。在裸鼠的瘤体上注射富勒烯-马来酸酐衍生物光敏剂,在500W 碘钨灯照射下,激发富勒烯产生大量的单线态氧,杀伤活性肿瘤,在光强为500W 碘钨灯,浓度为50ug/ml 时,裸鼠寿命平均延长6 天,瘤径减小0.5cm,瘤重减轻0.7 克,在活体水平上验证了富勒烯-马来酸酐衍生物的光动力学作用。另外,在离体的骨肿瘤细胞中加入细胞培养物和富勒烯-马来酸酐衍生物光敏剂,用碘钨灯照射激发富勒烯,经MTT 法检测,离体骨肿瘤细胞也明显被杀伤。富勒烯具有强的光敏剂作用,它不仅在活体水平上可以杀伤骨肉瘤而且对离体的骨肉瘤细胞也有很强的杀伤作用。 首次系统地研究了六类特定结构设计的水溶性富勒烯衍生物的体外抗癌活性。结果表明该水溶性富勒烯衍生物对人体的骨癌等癌细胞具有很好的抑制率。水溶性富勒
[Abstract]:Due to the unique chemical and physical properties of C60, the biological activities of fullerenes and their derivatives have attracted much attention in recent years. In this paper, the biological activity of fullerene derivatives was studied by means of macromolecule chemistry, organic chemistry and biology. The relationship between the structure of water-soluble fullerene derivatives and the photoinduced toxicity of cancer cells was studied by means of MTT and the mechanism of photo-induced toxicity of water-soluble fullerene derivatives was studied. Three kinds of water-soluble fullerene copolymers, that is, fullerene-vinyl pyrrolidone copolymers, fullerene-maleic anhydride copolymers and fullerene-acrylamide copolymers, were synthesized by free radical polymerization and molecular design. Three kinds of water-soluble fullerene derivatives, i.e. fullerene-lysine derivatives, fullerene-glycine derivatives and fullerene-aspartate derivatives, were synthesized by organic chemistry. They were prepared for the first time. These six fullerene derivatives are well dissolved in water. The reaction mechanism and reaction conditions of six water-soluble fullerene derivatives were studied for the first time. Their structures were characterized by gel permeation chromatography (GPC) GPC, UV UV, IR FTIR, NMR 1HNMR. The TEM morphology of the aqueous solution of fullerene derivatives was found to be ideal spherical by TEM analysis, and the average particle size was less than 50 nm. Compared with the TEM morphology of the homopolymer aqueous solution, the morphology of the corresponding aqueous solution was amorphous. In order to verify the photodynamic damage of aqueous fullerene derivatives to tumors in vivo, the photodynamic killing effects of fullerene-maleic anhydride derivatives on osteosarcoma in nude mice were studied for the first time. Fullerene-maleic anhydride derivative Guang Min was injected into the tumor of nude mice. Under the irradiation of 500W iodized tungsten lamp, fullerene produced a large amount of singlet oxygen to kill the active tumor. When the light intensity was 500W iodine tungsten lamp and the concentration was 50ug/ml, In vivo, the photodynamics of fullerene-maleic anhydride derivatives has been verified by prolonging the life of nude mice by an average of 6 days, reducing the diameter of the tumor by 0.5 cm and reducing the weight of the tumor by 0.7 g. In addition, cell cultures and fullerene-maleic anhydride derivative Guang Min were added to bone tumor cells in vitro. Fullerenes were stimulated by iodized tungsten lamp. The results of MTT assay showed that in vitro bone tumor cells were also significantly killed. Fullerene has strong effect of Guang Min, it can kill osteosarcoma not only in vivo, but also on osteosarcoma cells in vitro. The in vitro anticancer activity of six water soluble fullerene derivatives designed for specific structures was studied for the first time. The results showed that the water-soluble fullerene derivatives had a good inhibitory rate on human bone cancer and other cancer cells. Water-soluble Fulle
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R313
本文编号：2398020
[Abstract]:Due to the unique chemical and physical properties of C60, the biological activities of fullerenes and their derivatives have attracted much attention in recent years. In this paper, the biological activity of fullerene derivatives was studied by means of macromolecule chemistry, organic chemistry and biology. The relationship between the structure of water-soluble fullerene derivatives and the photoinduced toxicity of cancer cells was studied by means of MTT and the mechanism of photo-induced toxicity of water-soluble fullerene derivatives was studied. Three kinds of water-soluble fullerene copolymers, that is, fullerene-vinyl pyrrolidone copolymers, fullerene-maleic anhydride copolymers and fullerene-acrylamide copolymers, were synthesized by free radical polymerization and molecular design. Three kinds of water-soluble fullerene derivatives, i.e. fullerene-lysine derivatives, fullerene-glycine derivatives and fullerene-aspartate derivatives, were synthesized by organic chemistry. They were prepared for the first time. These six fullerene derivatives are well dissolved in water. The reaction mechanism and reaction conditions of six water-soluble fullerene derivatives were studied for the first time. Their structures were characterized by gel permeation chromatography (GPC) GPC, UV UV, IR FTIR, NMR 1HNMR. The TEM morphology of the aqueous solution of fullerene derivatives was found to be ideal spherical by TEM analysis, and the average particle size was less than 50 nm. Compared with the TEM morphology of the homopolymer aqueous solution, the morphology of the corresponding aqueous solution was amorphous. In order to verify the photodynamic damage of aqueous fullerene derivatives to tumors in vivo, the photodynamic killing effects of fullerene-maleic anhydride derivatives on osteosarcoma in nude mice were studied for the first time. Fullerene-maleic anhydride derivative Guang Min was injected into the tumor of nude mice. Under the irradiation of 500W iodized tungsten lamp, fullerene produced a large amount of singlet oxygen to kill the active tumor. When the light intensity was 500W iodine tungsten lamp and the concentration was 50ug/ml, In vivo, the photodynamics of fullerene-maleic anhydride derivatives has been verified by prolonging the life of nude mice by an average of 6 days, reducing the diameter of the tumor by 0.5 cm and reducing the weight of the tumor by 0.7 g. In addition, cell cultures and fullerene-maleic anhydride derivative Guang Min were added to bone tumor cells in vitro. Fullerenes were stimulated by iodized tungsten lamp. The results of MTT assay showed that in vitro bone tumor cells were also significantly killed. Fullerene has strong effect of Guang Min, it can kill osteosarcoma not only in vivo, but also on osteosarcoma cells in vitro. The in vitro anticancer activity of six water soluble fullerene derivatives designed for specific structures was studied for the first time. The results showed that the water-soluble fullerene derivatives had a good inhibitory rate on human bone cancer and other cancer cells. Water-soluble Fulle
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R313
【引证文献】
相关博士学位论文 前1条
1 江岸;Sm金属富勒烯的合成、分离、结构和衍生[D];浙江大学;2010年
，本文编号：2398020
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