氧化石墨烯基非共價(jià)修飾納米復(fù)合材料的制備及其在藥物遞送方面的應(yīng)用
發(fā)布時(shí)間:2018-06-18 02:33
本文選題:氧化石墨烯 + 層層自組裝; 參考:《江蘇大學(xué)》2017年碩士論文
【摘要】:癌癥一直是嚴(yán)重危害人類健康的一個(gè)話題,為了提高抗癌效率以及減輕治療過程中對(duì)機(jī)體的毒副作用,人們對(duì)此設(shè)計(jì)了許多藥物運(yùn)輸系統(tǒng)。其中,納米材料介導(dǎo)的藥物運(yùn)輸系統(tǒng)吸引了廣泛的關(guān)注。在眾多納米材料當(dāng)中,氧化石墨烯(GO)由于其具有水溶性,有較大的適于藥物負(fù)載的比表面積等優(yōu)異特性而被廣泛應(yīng)用于載藥領(lǐng)域。盡管氧化石墨烯有許多優(yōu)異特性,但其在生理?xiàng)l件下易聚集,因此,增強(qiáng)其在生理?xiàng)l件下的溶解性成為了解決問題的關(guān)鍵。其中,對(duì)GO進(jìn)行表面的修飾可以增強(qiáng)它在生理?xiàng)l件下的溶解性。層層自組裝技術(shù)是納米粒表面修飾的一個(gè)很重要的技術(shù),它主要是通過在納米粒子表面逐步沉積帶相反電荷的聚電解質(zhì)來形成殼核納米結(jié)構(gòu)。然而,在氧化石墨烯納米片層表面層層堆積帶電荷的聚合電解質(zhì)并將其作為抗癌藥物運(yùn)輸載體的研究仍然處在初始階段。在本論文中,我們分別用了兩個(gè)帶相反電荷的多聚電解質(zhì),殼聚糖(CS)和海藻酸鈉(SA),殼聚糖(CS)和葡聚糖(Dex),魚精蛋白(PRM)和海藻酸鈉(SA)作為膜材,利用層層自組裝技術(shù),分別合成了GO-CS-SA,GO-CS-Dex和GO-PRM-SA納米復(fù)合物。然后用FTIR、zeta電位和AFM等方法對(duì)其進(jìn)行表征,其次進(jìn)一步對(duì)復(fù)合物的穩(wěn)定性,非特異性蛋白吸附進(jìn)行研究。最后,對(duì)該納米復(fù)合物進(jìn)行抗癌藥物阿霉素(DOX)的負(fù)載,對(duì)其藥物負(fù)載,藥物釋放,以及細(xì)胞毒性行為進(jìn)行考察。具體研究結(jié)果如下:1.以GO為基體,帶有反向電荷的CS和SA、CS和Dex為聚電解質(zhì),通過層層自組裝技術(shù)分別合成了GO-CS-SA,GO-CS-Dex復(fù)合物。采用FTIR、AFM、Zeta電位、TGA等方法對(duì)其進(jìn)行表征,結(jié)果表明CS和SA,CS和Dex成功覆在了GO表面。穩(wěn)定性試驗(yàn)及非特異性蛋白吸附試驗(yàn)表明,CS/SA,CS/Dex的修飾不僅可以提高GO在生理?xiàng)l件下的分散性和穩(wěn)定性,而且降低了其非特異性蛋白吸附。2.藥物負(fù)載實(shí)驗(yàn)表明GO-CS-SA和GO-CS-Dex復(fù)合物均具有較高的藥物負(fù)載能力。藥物釋放實(shí)驗(yàn)發(fā)現(xiàn),負(fù)載有DOX的GO-CS-SA、GO-CS-Dex復(fù)合物展現(xiàn)出明顯的p H依賴特性的藥物釋放行為。通過細(xì)胞攝取實(shí)驗(yàn)發(fā)現(xiàn)兩種復(fù)合物均易被乳腺癌細(xì)胞(MCF-7)攝取,并主要分布在細(xì)胞質(zhì)中。細(xì)胞毒性實(shí)驗(yàn)表明單純的GO納米復(fù)合物對(duì)細(xì)胞沒有明顯毒性,載藥后的納米復(fù)合物對(duì)細(xì)胞則有顯著的細(xì)胞毒性作用。3.以GO,PRM和SA為原材料,通過物理吸附作用,使PRM和SA包覆在GO表面。將生成的GO-PRM-SA復(fù)合物通過FTIR、AFM、Zeta電位、TGA等表征手段對(duì)其進(jìn)行表征,結(jié)果表明PRM和SA成功負(fù)載在了GO表面。穩(wěn)定性試驗(yàn)及非特異性蛋白吸附試驗(yàn)表明,經(jīng)過PRM/SA修飾的GO不僅可以提高GO在生理?xiàng)l件下的分散性和穩(wěn)定性,而且降低了其非特異蛋白吸附。將該復(fù)合物進(jìn)行藥物負(fù)載,結(jié)果發(fā)現(xiàn)該復(fù)合物具有較高的藥物負(fù)載能力。藥物釋放實(shí)驗(yàn)發(fā)現(xiàn),負(fù)載有DOX的復(fù)合物展現(xiàn)出明顯的p H依賴特性的藥物釋放行為。最后MTT細(xì)胞毒性實(shí)驗(yàn)顯示負(fù)載DOX的GO-PRM-SA對(duì)MCF-7細(xì)胞具有顯著的細(xì)胞毒性作用。
[Abstract]:Cancer has been a subject of serious harm to human health. In order to improve the efficiency of cancer and to reduce the side effects of the body in the process of treatment, many drug transport systems have been designed. Among them, the drug transport system mediated by nanomaterials has attracted wide attention. Among the many nanomaterials, GO It is widely used in the field of drug loading because of its water-soluble and superior properties for drug loading. Although graphene oxide has many excellent properties, it is easily aggregated under physiological conditions. Therefore, enhancing its solubility under physiological conditions is the key to understanding the problem. Among them, the surface of GO is carried out. Modification can enhance its solubility under physiological conditions. Layer layer self-assembly technology is an important technique for the surface modification of nanoparticles. It is mainly formed by deposition of polyelectrolytes with opposite charges on the surface of nanoparticles to form a shell nanostructure. However, the layer of charge is stacked with charge on the surface of the graphite oxide nanometallic layer. In this paper, we used two polyelectrolytes with opposite charges, chitosan (CS) and sodium alginate (SA), chitosan (CS) and dextran (Dex), protamine (PRM) and sodium alginate (SA) as membrane materials, using layers self-assembly in this paper. Technology, GO-CS-SA, GO-CS-Dex and GO-PRM-SA nanocomposites were synthesized respectively. Then FTIR, zeta potential and AFM were used to characterize it. Secondly, the stability of the complex and non specific protein adsorption were further studied. Finally, the load of the anti-cancer drug doxorubicin (DOX) was carried out for the nanocomposite, and the drug load and drug were used. The results were as follows: 1. GO was used as the matrix, CS and SA with reverse charge, CS and Dex as polyelectrolytes, and GO-CS-SA and GO-CS-Dex complexes were synthesized by layers self-assembly. FTIR, AFM, Zeta potential and TGA were used to characterize them. The work was coated on the surface of GO. The stability test and the non specific protein adsorption test showed that the modification of CS/SA and CS/Dex could not only improve the dispersion and stability of GO under physiological conditions, but also reduced the non specific protein adsorption.2. drug loading experiment, which showed that both GO-CS-SA and GO-CS-Dex complexes had high drug loading ability. The release experiment showed that the load was DOX GO-CS-SA, and the GO-CS-Dex complex showed a distinct P H dependent drug release behavior. Through the cell uptake experiment, the two compounds were easily absorbed by breast cancer cells (MCF-7) and distributed mainly in the cytoplasm. The cytotoxicity test showed that pure GO nanocomposites were not available to the cells. The nano complex after carrying the drug has significant cytotoxic effect on the cell.3., GO, PRM and SA are used as the raw materials. By physical adsorption, PRM and SA are coated on the surface of GO. The resulting GO-PRM-SA complexes are characterized by FTIR, AFM, Zeta potential, TGA and other characterization methods. On the surface, the stability test and the nonspecific protein adsorption test showed that the PRM/SA modified GO could not only improve the dispersion and stability of GO under physiological conditions, but also reduced the adsorption of nonspecific protein. The compound was loaded with a high drug loading ability. It was found that the complex loaded with DOX showed a distinct P H dependent drug release behavior. Finally, the MTT cell toxicity test showed that the GO-PRM-SA loaded with DOX had significant cytotoxic effect on MCF-7 cells.
【學(xué)位授予單位】:江蘇大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:TB33;TQ460.1
【參考文獻(xiàn)】
相關(guān)碩士學(xué)位論文 前1條
1 王孝華;海藻酸鈉的提取及應(yīng)用研究[D];重慶大學(xué);2004年
,本文編號(hào):2033625
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