具標靶化之超順磁氧化鐵奈米粒子磁振造影對比劑之合成與特性研究

Abstract

本研究目的在於設計一功能性磁性奈米粒子，結合光學與磁振造影的雙功能對比劑，並可具體的對高侵略性的乳癌做早期的檢測。研究中以氧化鐵奈米粒子為核心，其裸核直徑為9.2 ± 0.8 nm，接著以兩性高分子聚合物PMAO-PEG修飾奈米粒子表面。PMAO為一平均分子量30000~50000之長碳鏈高分子，將PMAO和PEG反應後可形成雙極性並具有包覆能力之高分子聚合物，便可利用PMAO-PEG的特性修飾氧化鐵奈米粒子，增加奈米粒子之親水性及生物相容性，同時將螢光染劑Rhodamine B以包覆的形式，形成能做為MRI對比劑外亦能應用於光學影像之奈米探針。以60MHz relaxometer測量其橫向弛緩率，其橫向弛緩率為223.5 ± 5.7 mM-1s-1相較於市售之對比劑 ResovistTM之弛緩率 (164.5 ± 4.2 mM-1s-1) 高出許多。此外將NTR1抗體鍵結上PMAO-PEG外端裸露之COOH基團，做為偵測高轉移性的乳癌細胞表面上之NTR1蛋白。根據實驗結果，此一奈米探針之水合直徑為34.6 ± 0.6 nm，在共軛焦顯微鏡結果證實此奈米探針具有專一性鍵結能力，在MRI體外顯影上針對表面NTR1蛋白之細胞株獲得良好的對比影像。因此，本文研究已設計出用於乳癌的高度專一性的多功能磁性奈米粒子，可用於高侵略性乳癌的早期診斷。

This study aimed to design a functional magnetic nanoparticles, combined optical and magnetic resonance imaging of bifunctional contrast agent for specific and early detection of highly aggressive breast cancer. Iron oxide nanoparticles are used as contrast agent for MRI enhancement,and the diameter of the core is 9.2 ± 0.8 nm. The average of PAMO molecular weight is about 30,000 to 50,000 of long carbon chain polymers, will PMAO and PEG can be formed a bipolar polymers. We can take advantage of the characteristics of PMAO-PEG to modify iron oxide nano-particles, increasing the hydrophilic and biocompatibility of nanoparticels. The fluorescent dye Rhodamine B is loaded, which can be applied to the optical image. The transverse relaxation rate of nanoparticles is 223.5 ± 5.7 mM-1s-1, which is much higher than the commercially contrast agents ResovistTM (164 ± 4.2 mM-1s-1) by 60 mHz relaxometer. In addition to NTR1 antibody binding PMAO-PEG on the outer end of the exposed COOH group, as a specific target moiety to detected the NTR1 proteins on the surface of highly metastatic breast cancer cells. According to the experimental results, the final hydrated diameter of nanoparticles is 34.6 ± 0.6 nm, with specific binding ability by confocal images and in vitro MR images. Therefore, we has designed a high specificity multifunctional magnetic nanoparticles which can be used for detecting highly aggressive breast cancer in early stage.