本文選題：聚天冬氨酸 + 納米顆粒�。� 參考：《北京化工大學(xué)》2016年碩士論文

【摘要】：納米藥物傳遞系統(tǒng)(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質(zhì)、治療藥物、siRNA(小干擾RNA)等成分后,通過細(xì)胞吞噬作用被細(xì)胞攝入從而提高血液運(yùn)輸功能以及靶向治療。聚天冬氨酸(Polyaspartic Acid)作為人工合成的高分子生物材料,具有良好的生物相容性,并隨著主鏈的降解釋放出無毒無害的天然氨基酸成分。實(shí)體腫瘤細(xì)胞外呈弱酸性(pH值6.5-7.2),本文設(shè)計(jì)了一種以聚天冬氨酸為骨架,葉酸(FA)為分子靶向,具有pH值響應(yīng)性的自組裝聚天冬氨酸-組氨酸(FA-PASP-His)納米藥物載體。本文對FA-PASP-His納米粒進(jìn)行多方位的特性表征,經(jīng)驗(yàn)證得到納米顆粒的粒徑取決于組氨酸的取代度�？鼓[瘤藥物阿霉素(DOX)通過超聲分散和透析兩種方法包埋到載體中,體外藥物釋放表明DOX可以從pH敏感的納米粒中隨著pH值的變化控制釋放出來。除此之外,細(xì)胞毒性實(shí)驗(yàn)表明在pH值低于7.0時(相當(dāng)于腫瘤細(xì)胞內(nèi)生理pH值),DOX快速的從載藥納米粒中釋放出來同時具有很強(qiáng)的細(xì)胞毒性,并具具有緩釋效和一定的時間效應(yīng)。當(dāng)pH值高于7.0時(相當(dāng)于正常細(xì)胞內(nèi)生理pH值),載藥納米粒對細(xì)胞無毒副作用。同時,通過細(xì)胞流式儀(FCM)檢測細(xì)胞凋亡情況得出對于人宮頸癌細(xì)胞(HeLa)和人肝癌細(xì)胞(HepG2),載藥納米粒均對其細(xì)胞毒性高于自由藥物,并且體現(xiàn)出促進(jìn)癌細(xì)胞凋亡的效果,而納米粒本身并不具有細(xì)胞毒性。最后本文還通過細(xì)胞流式技術(shù)比較了未經(jīng)葉酸修飾的載藥納米粒和經(jīng)葉酸修飾的載藥納米粒,驗(yàn)證了葉酸優(yōu)良的靶向性。拓寬了載體材料聚天冬氨酸與靶向分子結(jié)合的研究基礎(chǔ)。
[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.
【學(xué)位授予單位】：北京化工大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：TB383.1;TQ460.4

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