本文選題：金屬有機(jī)骨架材料　切入點(diǎn)：超聲-攪拌法　出處：《哈爾濱理工大學(xué)》2017年碩士論文

【摘要】：金屬有機(jī)骨架材料(Metal-Organic Frameworks,MOFs)是由金屬離子與有機(jī)配體通過(guò)自組裝過(guò)程雜化生成的一類(lèi)具有周期性多維網(wǎng)狀結(jié)構(gòu)的多孔材料,在催化、傳感、氣體儲(chǔ)存和載藥等方面均表現(xiàn)出了優(yōu)異的性能。成為了科研人員研究的熱點(diǎn)。特別在載藥方面,由于其大的比表面積,以及較好的生物相容性已被科研人員定位良好的藥物載體。本文制備了三種生物相容性較好的納米MOFs藥物載體,進(jìn)而利用后合成修飾對(duì)藥物載體功能化,實(shí)現(xiàn)了藥物載體聯(lián)合載藥和潛在主動(dòng)腫瘤靶向性。本文利用超聲-攪拌法及優(yōu)化反應(yīng)條件制備了粒徑在300 nm以下的納米ZIF-90材料,利用傅里葉紅外光譜(FT-IR)、X-射線粉末衍射(XRD)確定了其結(jié)構(gòu),掃描電子顯微鏡(SEM)確定了大小形貌。進(jìn)而利用ZIF-90配體中醛基與抗腫瘤藥物阿霉素(DOX)中氨基進(jìn)行縮合反應(yīng),將DOX修飾在ZIF-90納米材料表面,利用固體核磁碳譜、FT-IR、熱重(TGA)確定了DOX成功修飾。對(duì)納米藥物載體DOX@ZIF-90裝載和釋放抗癌藥物5-氟尿嘧啶(5-Fu)進(jìn)行了研究,該納米藥物載體的裝載5-Fu能力最高可達(dá)0.572 g/g;由于ZIF-90的p H不穩(wěn)定性,使得在腫瘤組織處釋放時(shí),DOX的釋放量為0.45g/g,5-Fu的釋放率達(dá)到95%以上。并且該藥物載體是首個(gè)基于MOFs材料實(shí)現(xiàn)聯(lián)合裝載兩種抗腫瘤藥物的載體。通過(guò)加熱回流攪拌法及優(yōu)化反應(yīng)條件制備了納米PCN-223與納米MOF-808材料,利用FT-IR、XRD確定了其結(jié)構(gòu),SEM確定了各自的形貌和大小,進(jìn)一步利用靶向制劑葉酸(FA)通過(guò)配位作用修飾在了PCN-223與MOF-808材料上,利用固體核磁碳譜、FT-IR、TGA和紫外可見(jiàn)光譜(UV-vis)并對(duì)其裝載和釋放抗腫瘤藥物5-Fu進(jìn)行了研究。結(jié)果表明FA@PCN-223材料裝載5-Fu最高可達(dá)0.654 g/g,釋放率為80.14%;FA@MOF-808材料裝載5-Fu最高可達(dá)0.846 g/g,釋放率為78.13%。該藥物載體是首次通過(guò)配位作用實(shí)現(xiàn)MOFs材料潛在主動(dòng)腫瘤靶向藥物載體。
[Abstract]:Metal-Organic frameworks (MOFs) is a kind of porous materials with periodic multi-dimensional network structure formed by self-assembly of metal ions and organic ligands. Gas storage and drug loading have shown excellent performance. It has become a hot spot in scientific research. Especially in drug loading, due to its large specific surface area, In this paper, three kinds of nano-scale MOFs drug carriers with good biocompatibility were prepared, and then the drug carriers were functionalized by post-synthetic modification. The drug carrier combined drug loading and potential active tumor targeting were realized. In this paper, nanocrystalline ZIF-90 materials with particle size less than 300nm were prepared by ultrasonic stirring method and optimized reaction conditions. The structure was determined by Fourier transform infrared spectroscopy (FT-IR) and the morphology was determined by scanning electron microscopy (SEM). Furthermore, the condensation reaction of aldehydes in ZIF-90 ligands with amino groups in the anti-tumor drug doxorubicin (DOX) was carried out. DOX was modified on the surface of ZIF-90 nanomaterials. The DOX modification was confirmed by solid nuclear magnetic resonance spectroscopy (FT-IR) and thermogravimetric analysis (TGA). The loading and release of 5-fluorouracil (5-Fu), an anticancer drug, was studied on the nano-drug carrier DOX@ZIF-90. The 5-Fu loading capacity of the nano-drug carrier can be up to 0.572 g / g. Due to the pH instability of ZIF-90, The release rate of dox is more than 95% when released in tumor tissue, and the drug carrier is the first to carry two kinds of antitumor drugs based on MOFs material. Nano PCN-223 and nano MOF-808 materials were prepared under optimized reaction conditions. The morphology and size of the two materials were determined by FT-IR XRD. Furthermore, the PCN-223 and MOF-808 materials were modified by coordination reaction with the targeted preparation folate. The loading and release of antitumor drug 5-Fu were studied by means of solid nuclear magnetic resonance carbon spectroscopy FT-IRGA-TGA and UV-vis-vis spectra. The results show that the maximum loading of 5-Fu in FA@PCN-223 materials can be up to 0.654 g / g, and the release rate is 80.14% FAMOF-808 with 5-Fu loading up to 0.846 g / g, and the release rate is up to 0.846 g / g. The drug carrier is the first potential active tumor targeting drug carrier of MOFs material through coordination.
【學(xué)位授予單位】：哈爾濱理工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：TQ460.1;TB383.1

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本文編號(hào)：1655698