【摘要】：由于C_(60)獨特的化學和物理特性,富勒烯及其衍生物的生物活性近年來引起了人們的注意。本論文利用高分子化學、有機化學和生物學的方法對富勒烯衍生物的生物活性這一交叉課題進行了研究。通過MTT 等方法,系統(tǒng)地研究了水溶性富勒烯衍生物的結(jié)構與其光誘導的癌細胞毒性功能的關系,并較深入地研究了水溶性富勒烯衍生物光誘導的癌細胞毒性的作用機理。 采用高分子的自由基聚合及分子設計的方法,合成了三種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-馬來酸酐共聚物,富勒烯-丙烯酰胺共聚物。采用有機化學的方法合成了三種水溶性富勒烯衍生物,即富勒烯-賴氨酸衍生物,富勒烯-甘氨酸衍生物,富勒烯-天門冬氨酸衍生物。它們?yōu)槭状沃苽�。這六個富勒烯衍生物均能很好的溶解在水中。 首次研究了六個水溶性富勒烯衍生物的反應機理及反應條件。并采用凝膠滲透色譜GPC、紫外光譜UV、紅外光譜FTIR、核磁共振1HNMR 等分析方法對它們進行了結(jié)構表征。利用透射電鏡分析發(fā)現(xiàn)富勒烯衍生物水溶液的TEM 形貌均為理想的球形,其數(shù)均粒徑均小于50nm,與之相比,相應均聚物水溶液的TEM 形貌為無定形狀。 為驗證水溶液富勒烯衍生物對活體腫瘤的光動力學損傷作用,我們首次進行了動物體內(nèi)實驗:富勒烯-馬來酸酐衍生物對裸鼠的骨肉瘤的光動力學殺傷作用。在裸鼠的瘤體上注射富勒烯-馬來酸酐衍生物光敏劑,在500W 碘鎢燈照射下,激發(fā)富勒烯產(chǎn)生大量的單線態(tài)氧,殺傷活性腫瘤,在光強為500W 碘鎢燈,濃度為50ug/ml 時,裸鼠壽命平均延長6 天,瘤徑減小0.5cm,瘤重減輕0.7 克,在活體水平上驗證了富勒烯-馬來酸酐衍生物的光動力學作用。另外,在離體的骨腫瘤細胞中加入細胞培養(yǎng)物和富勒烯-馬來酸酐衍生物光敏劑,用碘鎢燈照射激發(fā)富勒烯,經(jīng)MTT 法檢測,離體骨腫瘤細胞也明顯被殺傷。富勒烯具有強的光敏劑作用,它不僅在活體水平上可以殺傷骨肉瘤而且對離體的骨肉瘤細胞也有很強的殺傷作用。 首次系統(tǒng)地研究了六類特定結(jié)構設計的水溶性富勒烯衍生物的體外抗癌活性。結(jié)果表明該水溶性富勒烯衍生物對人體的骨癌等癌細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
【學位授予單位】：華中科技大學
【學位級別】：博士
【學位授予年份】：2005
【分類號】：R313

【引證文獻】

相關博士學位論文 前1條

1 江岸;Sm金屬富勒烯的合成、分離、結(jié)構和衍生[D];浙江大學;2010年

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本文編號：2398020