Aptamers as Targeting Ligands in Thromboembolic Theranostics( I )

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Project title

Code/計畫編號

MOST109-2124-M182-001

Translated Name/計畫中文名

核酸適體應用於標靶血栓的診斷與治療(1/3)

Funding Organization/主管機關

National Science and Technology Council

Co-Investigator(s)/共同執行人

馬蘊華(計畫主持人)
陳志平
賴文福
林彥伶

Department/Unit

Department of Physiology and Pharmacology,CGU

Website

https://www.grb.gov.tw/search/planDetail?id=13538483

Year

2020

Start date/計畫起

01-08-2020

Expected Completion/計畫迄

31-07-2021

Co-Investigator(s)

Chih-Ching Huang

Bugetid/研究經費

6500千元

ResearchField/研究領域

其他（醫）

以胞漿素原活化劑(plasminogen activator)降解血栓仍然是臨床上栓塞急性期不使用手術而使血流回復、避免組織壞死最主要的治療策略，然而使用重組胞漿素原活化劑(rtPA)所產生流血不止的副作用侷限其應用。由於第十三凝血因子(FXIII)為參與凝血過程最後一個凝血因子，且其活化態亦表現於活化的血小板膜上，本團隊採用指數富集配體之系統進化技術(SELEX)由單股去氧核醣核酸庫中篩選出對活化之第十三凝血因子(FXIII)具有高親和性之適配體(aptamer), 因此擬於本計畫中測試以下假說: 對FXIII具有高親和性之適配體可同時標靶血栓中兩種主要成分- 活化的血小板及纖維蛋白。在此計畫中，團隊擬將此適配體做為標靶配體，結合於三個系列的rtPA奈米級複合物，包括氧化鐵磁粒子(MNPs)、金/石墨烯複合物(Au/GO)及磁微脂體(magnetoliposome)，並進一步測試其作為顯影成像以標靶、辨識體內血栓的潛力。本跨領域、跨單位合作計畫由材料、藥理、臨床影像等領域學者及醫師參與，期望發展可用於標靶血栓的診斷工具及攜藥載體。本計畫擬:目標1: 最適化標靶第十三凝血因子之適配體並研究其特性目標2: 製備標靶第十三凝血因子之奈米載體用於胞漿素原活化劑輸送目標3: 決定標靶第十三凝血因子之奈米藥物的溶栓效價目標4: 以磁振造影(MRI)及電腦斷層掃描(CT)決定奈米藥物的標靶效應及溶栓作用 Plasminogen activator-induced thrombolysis is still the major strategy to restore blood flow and avoid tissue necrosis without requirement of surgical intervention in acute clinical setting. However, hemorrhagic adverse effects of the drug, recombinant tissue-type plasminogen activator (rtPA), limit its application. We have identified single strand DNA (ssDNA) sequence with high affinity to activated coagulation factor XIII (FXIIIa) using systematic evolution of ligands by exponential enrichment (SELEX) technology from ssDNA library; we thus hypothesize that this FXIIIa-specific aptamer may serve as an effective targeting ligand for both activated platelets and fibrin polymer in the thrombus. Three series of rtPA nanocomposites will be prepared and characterized, including magnetic nanoparticles (MNPs) with PLGA coating, Au nanoparticles-decorated graphene oxide nanocomposites and magnetoliposomes. The iron oxide-containing MNPs may also serve as contrast agents with magnetic resonance imaging at T2 mode; whereas Au nanoparticles may be visualized with computed tomography. This cross disciplinary team is composed of members with different expertise covering all areas required for this proposal. Experiments will be designed first, to develop FXIIIa-binding probes for thrombus imaging and targeting, and second, to develop FXIIIa-binding nanocomposites for targeted thrombolysis. Specific Aims are proposed:Aim 1- to optimize and characterize FXIII-targeting aptamersAim 2- to prepare and characterize FXIII-targeting nanocomposites for rtPA deliveryAim 3- to determine the thromolytic efficacy of the nanocompositesAim 4- to determine targeting/thrombolytic effects with MRI/CT

Keyword(s)

標靶藥物輸送
血栓溶解
奈米粒子
胞漿素原活化劑
第十三凝血因子
適配體
targeted drug delivery
thrombolysis
nanoparticles
plasminogen activators
coagulation factor XIII
aptamer

DSpace CRIS

Aptamers as Targeting Ligands in Thromboembolic Theranostics( I )

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