三功能性氧化釓摻雜銪結合核酸適體之奈米粒子應用於核磁共振/斷層掃描/螢光 分子影像研究

Abstract

開發單一奈米材料兼具多功能之應用價值是目前奈米生醫領域研究與探討的課題。本文製備同時具有螢光、核磁共振訊號與X-ray吸收特性的多功能性奈米粒子-氧化釓摻雜銪，接著在奈米粒子外面包覆核酸適體（aptamer），希望透過其專一性的表現而能應用於分子影像顯影。 首先經由多元醇法合成出氧化釓摻雜銪的奈米粒子，並且以TEM、XRD、UV-PL、SQUID與EDS等儀器來加以分析與鑑定。接著再以FT-IR、TGA和 zetasizer來鑑定氧化釓摻雜銪奈米粒子表面修飾之檸檬酸基。最後則是透過qPCR 和confocal 來說明核酸適體的確有與我們所合成之奈米粒子結合。 將氧化釓摻雜銪奈米粒子應用於in vitro MRI上，經由實驗可得其 r1為5.0199 s-1mM-1，相比於T1-MRI常用之釓金屬類錯合物顯影劑如Gd-DOTA、Gd-DTPA（r1皆為4.1s-1mM-1）有較高的relaxivity，表示其MRI對比顯影效果較佳；而在in vitro CT的應用上，在重量濃度為350毫克/每毫升時，氧化釓摻雜銪奈米粒子的HU值高於常用之CT含碘顯影劑IOHEXOL，但低於350毫克/每毫升時，其HU值仍是低於含碘顯影劑IOHEXOL。Recent nano-biomedicine have devote to research the topics for the development of single nano-materials possessing multifunctional properties. In this thesis, we synthesized the multifunctional europiumdoped gadolinium oxide ( Gd2O3:Eu ) nanoparticles which equipped with fluorescence, magnetic resonance signal and X-ray absorption. Then we applied the specific targeting aptamer encapsulated outside the nanoparticles for molecular imaging. First, Gd2O3:Eu nanoparticles were synthesized via the polyol method and were characterized based on TEM, XRD, UV-PL, SQUID and EDS. Then we identified the surface capping ligand citric acid of Gd2O3:Eu nanoparticles through FT-IR, TGA, and zetasizer. Ultimately,we employed qPCR and confocal to confirm the binding of Gd2O3:Eu-AP nanoparticles. Gd2O3:Eu nanoparticles were applied on the in vitro MRI. Compared to the conventional T1 MRI gadolinium chelated complex such as Gd-DOTA、Gd-DTPA（r1 4.1s-1mM-1）, the relaxivity of Gd2O3:Eu nanoparticles（r1 5.0199s-1mM-1）was much higher. In other words, the effect of MRI enhanced contrast image by Gd2O3:Eu nanoparticles was better. On the in vitro CT, there was a much higher HU value of Gd2O3:Eu nanoparticles at the weight concentration of 350 mg/ml than the common CT iodine contrast agent IOHEXOL. But less than 350 mg/ml, the HU value of Gd2O3:Eu nanoparticles was still lower than IOHEXOL.