聚天冬氨酸自组装纳米颗粒的制备及载药研究

发布时间：2018-07-12 13:39

本文选题：聚天冬氨酸 + 纳米颗粒　；参考：《北京化工大学》2016年硕士论文

【摘要】：纳米药物传递系统(Nanopartiele drug delivery system, NDDS)是指人工合成的或天然形存在的生物大分子以及高分子聚合物包埋蛋白质、治疗药物、siRNA(小干扰RNA)等成分后,通过细胞吞噬作用被细胞摄入从而提高血液运输功能以及靶向治疗。聚天冬氨酸(Polyaspartic Acid)作为人工合成的高分子生物材料,具有良好的生物相容性,并随着主链的降解释放出无毒无害的天然氨基酸成分。实体肿瘤细胞外呈弱酸性(pH值6.5-7.2),本文设计了一种以聚天冬氨酸为骨架,叶酸(FA)为分子靶向,具有pH值响应性的自组装聚天冬氨酸-组氨酸(FA-PASP-His)纳米药物载体。本文对FA-PASP-His纳米粒进行多方位的特性表征,经验证得到纳米颗粒的粒径取决于组氨酸的取代度。抗肿瘤药物阿霉素(DOX)通过超声分散和透析两种方法包埋到载体中,体外药物释放表明DOX可以从pH敏感的纳米粒中随着pH值的变化控制释放出来。除此之外,细胞毒性实验表明在pH值低于7.0时(相当于肿瘤细胞内生理pH值),DOX快速的从载药纳米粒中释放出来同时具有很强的细胞毒性,并具具有缓释效和一定的时间效应。当pH值高于7.0时(相当于正常细胞内生理pH值),载药纳米粒对细胞无毒副作用。同时,通过细胞流式仪(FCM)检测细胞凋亡情况得出对于人宫颈癌细胞(HeLa)和人肝癌细胞(HepG2),载药纳米粒均对其细胞毒性高于自由药物,并且体现出促进癌细胞凋亡的效果,而纳米粒本身并不具有细胞毒性。最后本文还通过细胞流式技术比较了未经叶酸修饰的载药纳米粒和经叶酸修饰的载药纳米粒,验证了叶酸优良的靶向性。拓宽了载体材料聚天冬氨酸与靶向分子结合的研究基础。
[Abstract]:Nanopartiele drug delivery system, is a synthetic or natural form of biological macromolecules and polymer encapsulated proteins, therapeutic drugs such as siRNAs (small interfering RNAs). Cells ingest through phagocytosis to improve blood transport and target therapy. Polyaspartic Acid, as a synthetic polymer biomaterial, has good biocompatibility and releases non-toxic and harmless natural amino acid components with the degradation of the main chain. The extracellular acidity of solid tumor is weak (pH 6.5-7.2). In this paper, a novel self-assembled polyaspartic acid-histidine (FA-PASP-His) nano-drug carrier with polyaspartic acid as skeleton, folic acid (FA) as molecular target and pH response was designed. In this paper, the characteristics of FA-PASP-His nanoparticles were characterized in various directions. It was proved that the particle size of FA-PASP-His nanoparticles depended on the degree of substitution of histidine. The antitumor drug doxorubicin (DOX) was embedded in the carrier by ultrasonic dispersion and dialysis. The drug release in vitro indicated that DOX could be released from the pH sensitive nanoparticles with the change of pH value. In addition, cytotoxicity tests showed that DOX released rapidly from drug loaded nanoparticles when pH value was lower than 7.0 (corresponding to the physiological pH value of tumor cells), and had a slow release effect and a certain time effect. When the pH value was higher than 7.0 (corresponding to the physiological pH value of normal cells), the drug loaded nanoparticles had no toxic side effects on the cells. At the same time, the cell apoptosis was detected by flow cytometry (FCM). The results showed that the cytotoxicity of drug-loaded nanoparticles to human cervical cancer cells (HeLa) and human hepatoma cells (HepG2) was higher than that of free drugs, and it showed the effect of promoting cancer cell apoptosis. The nanoparticles themselves are not cytotoxic. Finally, we compared the unmodified nanoparticles with those modified by folic acid by flow cytometry, which proved the good targeting of folic acid. It broadens the research base of the binding of polyaspartic acid with target molecule.
【学位授予单位】：北京化工大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：TB383.1;TQ460.4

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