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Please use this identifier to cite or link to this item: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/53726

Title: 表沒食子兒茶素沒食子酸酯/魚精蛋白/褐藻醣膠自組裝奈米粒應用於預防巨噬細胞泡沫化
Prevention of foam cell fomation by epigallocatechin gallate/protamine/fucoidan self-assembly nanoparticles
Authors: Liu, Yun-Chun
劉芸君
Contributors: NTOU:Department of Food Science
國立臺灣海洋大學:食品科學系
Keywords: 褐藻醣膠;表沒食子兒茶素沒食子酸酯;自組裝奈米粒子;巨噬細胞;動脈粥狀硬化
Fucoidan;Epigallocatechin gallate;Self-assembled nanoparticles;Macrophage;Atherosclerosis
Date: 2019
Issue Date: 2020-07-03T08:43:12Z
Abstract: 心血管疾病是全球第一大死因,其中動脈粥狀硬化(atherosclerosis)所造成的慢性缺血性疾病為主要的病因,是由單核球細胞(monocytes)與內皮細胞的黏附分子互相作用產生黏附現象,隨之穿越內皮細胞層進入血管內膜趨化成巨噬細胞(macrophages),並持續攝取累積氧化低密度脂蛋白(oxidized low-density lipoprotein, Ox-LDL)後發炎形成泡沫細胞(foam cells),形成初始的動脈粥狀硬化,而結締組織會增生與修補,長期會產生硬化斑塊、若破裂會引起血小板活化形成血栓,持續進行則最終造成動脈阻塞,因此需使用具有抗氧化及抗發炎作用的藥物,來防止動脈硬化形成及預防心血管疾病發生,降低心血管疾病的死亡率,因此本研究使用褐藻醣膠(fucoidan)的抗血栓特性,表沒食子兒茶素沒食子酸酯(epigallocatechin gallate)之抗動脈粥狀硬化、抗發炎特性及魚精蛋白(protamine)之耐熱和拮抗特性,自組裝成表沒食子兒茶素沒食子酸酯/魚精蛋白/褐藻醣膠奈米粒(EGCG/Prot/Fu NPs);小分子量褐藻醣膠(low molecular weight fucoidan)具有更佳的抗凝血及抗血栓特性,亦自組裝成表沒食子兒茶素沒食子酸酯/魚精蛋白/小分子量褐藻醣膠奈米粒(EGCG/Prot/LMWF NPs),並藉由褐藻醣膠的標靶特性,準確傳送到發炎巨噬細胞的位置,且預防後續泡沫細胞之形成,進而評估此自組裝的奈米粒在防止血栓形成造成動脈粥狀硬化發生之效率。並藉 FTIR、TEM 證明本自組裝之兩種奈米載體具穩定性質,EGCG/Prot/Fu NPs及EGCG/Prot/LMWF NPs平均粒徑分別為 228、195 nm,界面電位為 -38、-35 mV,負電表明載體表面為褐藻醣膠居多,可賦予載體具有標靶至發炎細胞之位置,而此奈米粒具 pH 敏感性,尤其EGCG/Prot/Fu NPs,經光穿透分析證明此載體在酸性環境時型態穩定,因此具有口服藥物之潛力。實驗證明EGCG/Prot/Fu NPs與人類單核球巨噬細胞(human monocytic macrophage cell, THP-1 macrophages)及老鼠巨噬細胞(murine macrophages, RAW264.7)具有良好的生物相容性,顯微鏡觀察下,細胞與載體染色證明EGCG/Prot/Fu NPs具有預防泡沫細胞形成之效果,且可抑制巨噬細胞發炎;經由螢光顯微鏡觀察,表明巨噬細胞具有會此奈米粒的潛力,因此若發展奈米粒包覆具有抗心血管之藥物,可準確標靶在發炎的血管上預防泡沫細胞形成,有望發展為標靶治療的奈米粒,並作為預防動脈粥狀硬化之口服藥物載體。
Cardiovascular disease (CVD) is the number one cause of death worldwide. Ischemic heart diseases caused by atherosclerosis and majorly by the interaction of monocytes and adhesion molecules of endothelial cells. Then monocytes penetrate the endothelial cell layer into the vascular intima to become macrophages, and continue to uptake oxidized low-density lipoprotein. The connective tissue was proliferated and repaired, then produced atherosclerotic plaque for a long time. It caused platelet activation to the thrombus when it ruptured, finally it form to arterial occlusion. The drugs have anti-oxidant and anti-inflammatory properties can prevent arteriosclerosis, cardiovascular disease and reduce cardiovascular mortality, therefore this study used epigallocatechin gallate (EGCG), protamine (Prot), and fucoidan (Fu) to produce a self-assembled nanoparticles. Low molecular weight fucoidan (LMWF) has better anticoagulant and antithrombotic properties, also was used to produce self-assembled EGCG/Prot/LMWF nanoparticle. The Fu and LMWF-modified nanoparticles can target inflammatory macrophages to prevent the formation of foam cells. FTIR (fourier transform infrared spectroscopy) and TEM (transmission electron microscopy) were used to characterize the nanoparticles. The EGCG/Prot/Fu and EGCG/Prot/LMWF nanoparticles have average diameter of 228 nm and 195 nm, and negative zeta potentials (-38 mV and -35 mV), respectively. This indicated that the nanoparticle surface was covered by negatively charged fucoidan, thus enabling the nanoparticles to target inflammatory macrophages. Furthermore, the nanoparticles were pH sensitive, which can be used to control drug release at the acidic inflammatory microenvironment. Especially, light transmittance analysis proved the similar results, thus they have potential to be used as oral drug delivery system. Biocompatibility of the self-assembled nanoparticles on THP-1 macrophages and RAW264.7 was proved by MTT assay. Oil red O stain demonstrated that the nanoparticles could prevent the formation of foam cells and inhibit macrophage inflammation. Fluorescence microscopy demonstrated that the nanoparticles potential could target to macrophages. The nanoparticles can have potential to deliver anti-atherosclerosis drug and can accurately target and inhibit the formation of foam cells on blood vessels.
URI: http://ethesys.lib.ntou.edu.tw/cgi-bin/gs32/gsweb.cgi?o=dstdcdr&s=G0010632044.id
http://ntour.ntou.edu.tw:8080/ir/handle/987654321/53726
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