本文關(guān)鍵詞： PAMAM樹枝狀分子 動脈粥樣硬化成像 動脈粥樣硬化治療 光敏感　出處：《吉林大學(xué)》2016年博士論文　論文類型：學(xué)位論文

【摘要】：近30年來,心腦血管疾病的發(fā)病率一直居高不下,嚴重危害著人類生命健康,而作為誘發(fā)心腦血管疾病的重要病理基礎(chǔ)——動脈粥樣硬化還有很多研究的空間,雖然現(xiàn)在對動脈粥樣硬化這種疾病的診斷與治療手段已經(jīng)成型,但目前的診療手段都存在一定的滯后性,若能在疾病的早期及時發(fā)現(xiàn)病患并加以治療,將會大大的減少該疾病所帶來的危害。因此,我們針對這一問題,設(shè)計并合成了多種多功能診療納米粒子體系,并對各種體系的合成及性能作測試與表征,具體有如下工作:利用發(fā)散法合成了星形PAMAM樹枝狀分子,之后對合成的樹枝狀分子進行修飾,得到了不同的PAMAM配體,帶有配體的樹枝狀分子可以和氧化鐵納米粒子或者量子點等發(fā)生配體交換反應(yīng),在改變其溶解性的同時,還能夠保持其原有的光學(xué)性質(zhì)或超順磁性,且保持較小的粒徑,為后續(xù)的多功能修飾提供了基礎(chǔ)。通過雙羧基PEG為橋接,將靶向動脈粥樣硬化處MPO的靶分子5-羥色胺(5-HT)鏈接至G3.0 PAMAM表面,將造影劑Gd通過DTPA的絡(luò)合作用接入上述分子,再通過配體交換將產(chǎn)物交換到氧化鐵納米粒子表面,從而構(gòu)成了T1、T2復(fù)合靶向性核磁造影診斷體系。針對動脈粥樣硬化的病理特點,選用對光敏感的臨硝基芐基作為藥物釋放開關(guān),將治療動脈粥樣硬化藥物氟伐他汀通過臨硝基芐基連接至G3.0 PAMAM上,在特定波長光照下,統(tǒng)計其藥物釋放水平,結(jié)果證明了該體系作為光敏藥物釋放體系具有較高的藥物釋放率。本論文所設(shè)計并合成的多功能診療體系針對動脈粥樣硬化的早期診斷與治療具有很重要的潛在價值。
[Abstract]:In recent 30 years, the incidence of cardiovascular and cerebrovascular diseases has been high, seriously endangering human life and health. As an important pathological basis to induce cardiovascular and cerebrovascular diseases, there is still a lot of room for research on atherosclerosis, although the diagnosis and treatment of this disease has taken shape. However, the current diagnosis and treatment methods have a certain lag, if the disease can be found in the early and timely treatment, will greatly reduce the harm caused by the disease. Therefore, we aim at this problem. A variety of multifunctional nanoparticle systems for diagnosis and treatment were designed and synthesized, and the synthesis and properties of these systems were tested and characterized. The main work is as follows: star PAMAM dendrimer was synthesized by divergence method. The dendritic molecules were modified to obtain different PAMAM ligands. The dendrimers with ligand could exchange ligand with iron oxide nanoparticles or quantum dots. While changing its solubility, it can also maintain its original optical properties or superparamagnetism, and maintain a smaller particle size, which provides the basis for the subsequent multifunctional modification, which is bridged by dicarboxylic PEG. The target molecule of MPO targeted at atherosclerosis, 5-HT), was linked to the surface of G3.0 PAMAM, and the contrast agent Gd was connected to the molecule by the complexation of DTPA. Then the product was exchanged to the surface of iron oxide nanoparticles by ligand exchange, which formed the diagnostic system of T1T2-targeted nuclear magnetic resonance imaging, aiming at the pathological characteristics of atherosclerosis. The photo-sensitive p-nitrobenzyl group was selected as the drug release switch, and fluvastatin was connected to G 3.0 PAMAM through the p-nitrobenzyl group for the treatment of atherosclerosis under specific wavelength illumination. Count the drug release level. The results show that this system has high drug release rate as a drug release system of Guang Min. The multifunctional diagnosis and treatment system designed and synthesized in this paper has important potential for early diagnosis and treatment of atherosclerosis. Value.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R543.5;TB383.1

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本文編號：1482850