超順磁性氧化鐵奈米粒子鍵結8G7之磁振造影研究

Abstract

本論文的主要目的為發展高靈敏度的MRI對比劑以應用於胰腺癌的早期診斷。我們結合奈米技術與生物技術以設計 T2 weighted MRI對比劑。在超順磁性氧化鐵奈米粒子（SPION）的表面修飾 mPEG –NH2，其游離端可與 8G7 mAb鍵合，而這抗體對MUC4具有高專一性的特質。MUC4會有異常表現於胰腺癌，而正常胰腺與慢性胰腺炎則無。利用動態光散射儀（DLS）檢測SPIO-mPEG-NH2 和SPIO-mPEG-8G7奈米粒子的流體力學的平均粒徑分佈，分別為 37.7和45.9nm。SPIO-mPEG-8G7 在37.0 ± 0.1 ◦C和20 MHz測到的 relaxivity值，r1 和 r2，是24.97和206.01 mM-1s-1。由於SPIO-mPEG–8G7奈米粒子的標靶能力已藉由in vitro MRI證實, 因此在有表現 MUC4 的細胞株，SPIO-mPEG - 8G7奈米粒子可表現出顯著的磁共振對比。此外，利用MPCVD合成之石墨奈米薄片（GNSs）具高產率。其結構用掃描電子顯微鏡，透射電子顯微鏡，選擇區域電子衍射，X光衍射和拉曼光譜於做結構的分析。而目前以利用純碳作為T2 MRI對比劑的實驗還在持續進行中。

The primary objective of this thesis is to develop highly sensitive MRI contrast agent for early diagnosis of pancreatic cancer. We have exploited the novel aspects of nanotechnology and biotechnology to design T2 weighted MRI contrast agent. The superparamagnetic iron oxide nanoparticles (SPIONs) surface modified with mPEG-NH2 free terminal has been conjugated with 8G7 mAb, which is highly specific to MUC4. MUC4 is abruptly expressed in pancreatic cancer with no detectable expression in normal pancreas or chronic pancreatitis. The average hydrodynamic size distribution of SPIO-mPEG-NH2 and SPIO-mPEG-8G7 nanoparticles obtained by dynamic light scattering (DLS) are 37.7 and 45.9 respectively. The relaxivity values, r1 and r2, for the SPIO-mPEG-8G7 measured at 37.0 ± 0.1 ◦C and 20 MHz of are 24.97 and 206.01 mM-1s-1, respectively. The targeting ability of SPIO-mPEG-8G7 nanoparticles was confirmed by in vitro magnetic resonance imaging (MRI) study. SPIO-mPEG-8G7 nanoparticles show noticeable magnetic resonance contrast in phantom containing cell line expressing MUC4. In addition, graphene nanosheets (GNSs) were synthesized in high yield by MPCVD. The structure was characterized by scanning electron microscopy, transmission electron microscopy, selective area electron diffraction pattern, x-ray diffraction, and Raman spectroscopy. The experiments are in progress to develop pure carbon based T2 MRI contrast agent.