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Please use this identifier to cite or link to this item: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/48771

Title: 自組裝適合體修飾氧化石墨烯之抗凝血奈米藥劑
Self-Assembled Hybrid Aptamer Modified Graphene Oxide as an Anticoagulant Nanodrug
Authors: Lai, Pei-Xin
賴佩欣
Contributors: 國立臺灣海洋大學:生命科學暨生物科技學系
Keywords: 自組裝;適合體;氧化石墨烯;凝血酶;抗凝血
self-assembly;aptamers;graphene oxides;thrombin;anticoagulation
Date: 2016
Issue Date: 2018-08-22T06:31:10Z
Abstract: 氧化石墨烯(Graphene oxide, GO)具有許多獨特的物理性能,例如高表面積,優異的導電性和優良的機械強度。氧化石墨烯藉由凡得瓦力(van der Waals' force)、鹼基堆疊作用力(π-π stacking interaction)和氫鍵作用力(hydrogen bonding interaction)可吸附單股核酸鏈。在此,我們利用凝血酶結合適合體(thrombin-binding-aptamer 15 and 29, TBA15/29)於GO(〜230 nm)表面耦合自組裝成適合體單層(self-assembled hybrid monolayer)。TBA的第一段具單股腺嘌呤 [poly(adenine)] 可與GO表面作用鍵結;第二段則是可和另一TBA互補雜合(hybridize)的核苷酸;第三段分別是由15個與29個鹼基組成的專一辨識凝血酶之適合體(TBA15 and TBA29),提供與凝血酶的雙價作用結合(bivalent binding)。自組裝之三段式TBA具有可以調控TBA15和TBA29的最佳立體空間與適合體在GO表面上的密度(A20h20T5P4TBA15/29–GO, 簡稱TBA15/29–GO)。以上這些特性增強了與凝血酶的相互作用,增強其抗凝血的效果。在凝血酶凝固時間測試證明TBA15/29–GO的抗凝血效果較市售抗凝血藥物肝素(heparin)、阿加曲班(argatroban)、水蛭素(hirudin)及華法林(warfarin) 高出10倍以上。此外,在鼠尾出血時間測定也進一步證實了自組裝TBA15/29–GO抗凝效果約為肝素的兩倍。我們的研究結果證實TBA15/29–GO對於治療各種凝血疾病具有很好的應用潛力。
Graphene oxide (GO) possesses many unique physical properties such as high surface area, superior electric conductivity and excellent mechanical strength. Graphene oxide has been demonstrated that can effectively adsorb single-strand DNA mainly through π-π stacking, hydrogen-bonding interactions and hydrophobic interactions. Herein, we developed a thrombin-binding aptamer 15 and 29–conjugated GO (TBA15/29–GO), prepared from a self-assembled hybrid monolayer (SAHM) of triblock aptamers on GO (~230 nm), can effectively inhibit thrombin activity toward fibrinogen. The first block poly (adenine) at the end of the triblock TBA was used for the self-assembly on GO surface. The second block, in the middle of TBA, was composed of oligonucleotides that could hybridize with each other. The third block, containing TBA15 (15-base, binding to the exosite I of thrombin) and TBA29 (29-base, binding to the exosite II of thrombin) provided bivalent interaction with thrombin. The self-assembly aptamers have optimal distances between TBA15 and TBA29, aptamer density, and orientation on the GO surfaces. These properties strengthen the interactions with thrombin, resulting in an extremely high anticoagulant potency. The dose-dependence of thrombin clotting time (TCT) delay caused by TBA15/29–GO nanosheets is 10 times higher than commercially available drugs (heparin, argatroban, hirudin or warfarin). In addition, the rat–tail bleeding assay time further demonstrated the self-assembly TBA15/29–GO nanosheets were superior (~ 2-fold) to heparin. Our results suggested the TBA15/29–GO nanosheets possess good potential for the treatment of various diseases related to blood-clotting disorders.
URI: http://ethesys.lib.ntou.edu.tw/cgi-bin/gs32/gsweb.cgi?o=dstdcdr&s=G0010236043.id
http://ntour.ntou.edu.tw:8080/ir/handle/987654321/48771
Appears in Collections:[生命科學暨生物科技學系] 博碩士論文

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