轴向改性卟啉在光动力治疗的研究

发布时间：2018-08-12 16:54

【摘要】：光动力疗法(PDT)是一种区别于传统治疗肿瘤的方法,其基本原理是肿瘤患者注射光敏剂药物后,药物能够靶向富集于肿瘤组织周围,在一定波长的光照条件下,光敏剂药物吸收光能后激发与肿瘤周围组织氧作用,生成活性较高的单线态氧,单线态氧最终诱导肿瘤细胞死亡,达到治疗肿瘤目的。由于光敏剂具有肿瘤靶向性差、分子之间易聚集等缺陷限制了其在PDT中的应用。为了解决这些问题,本文开展具有轴向性、生物靶向性锡卟啉类光敏剂的研究。本文首先采用Adler法制备了四苯基卟啉,通过吡啶法得到轴向四苯基锡卟啉,Sn Cl2·2H2O提供金属配体,然后接枝丙二酸和乙酰化氨基葡萄糖;其次用浓H2SO4为磺化剂磺化四苯基卟啉得到四(4-磺酸基苯基)卟啉,通过甲醇法得到金属锡配位卟啉,接枝透明质酸得到轴向四(4-磺酸基苯基)锡卟啉-透明质酸。这两种轴向卟啉其结构通过核磁共振氢谱(1H NMR)、紫外可见光谱(UV-Vis)和红外光谱(FT-IR)等进行表征。最后,以1,3-二苯基异苯并呋喃(DPBF)作为单线态氧的捕获剂测定两种物质的单线态氧量子产率。结果表明,这两种卟啉类光敏剂能够产生较高的单线态氧,产率分别为0.68和0.73。说明轴向配位可以有效的解决卟啉分子间的自聚,保证了单线态氧的产率。所以,在生物医学领域里具有潜在的应用价值。
[Abstract]:Photodynamic therapy (PDT) is different from traditional methods in the treatment of tumor. Its basic principle is that after the tumor patients are injected with Guang Min, the drug can be targeted around the tumor tissue and be exposed to light at a certain wavelength. The drug of Guang Min stimulates the action of oxygen around the tumor tissue after absorbing the light energy and produces the highly active singlet oxygen which eventually induces the death of tumor cells and achieves the purpose of treating tumor. The application of Guang Min in PDT is limited due to its poor tumor targeting and easy aggregation among molecules. In order to solve these problems, the axial and biologically targeted tin porphyrin (Guang Min) agents have been studied in this paper. In this paper, tetraphenylporphyrin was prepared by Adler method. The tetraphenyltin porphyrin Sn Cl2 2H2O was prepared by pyridine method and then grafted with malonic acid and acetylated glucosamine. Tetra (4-sulfophenyl) porphyrin was obtained by sulfonation of tetraphenylporphyrins with concentrated H2SO4 as sulfonation agent. Metalloporphyrins were synthesized by methanol method, and tetra-( 4-sulfophenyl) tin porphyrin-hyaluronic acid was grafted onto hyaluronic acid to obtain tetra- (4-sulfophenyl) tin porphyrin-hyaluronic acid. The structures of these two kinds of porphyrins were characterized by 1H NMR), UV-Vis (UV-Vis) and IR (FT-IR) spectra. Finally, the single-line oxygen yields of two kinds of substances were determined by using 1 ~ 3- diphenyl isobenzofuran (DPBF) as the trapping agent of singlet oxygen. The results show that the two porphyrin Guang Min agents can produce higher singlet oxygen with the yields of 0.68 and 0.73, respectively. The results show that axial coordination can effectively solve the self-polymerization of porphyrin molecules and ensure the yield of singlet oxygen. Therefore, it has potential application value in biomedical field.
【学位授予单位】：长春理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R943

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