探討雙標的性超順磁氧化鐵奈米粒子SPIO-mPEG-Cy-TE777-Ab之合成、特性及其在磁振造影上之應用

Abstract

本研究中的以高溫裂解法合成了高弛緩率之超順磁氧化鐵-錳奈米粒子，其裸核直徑為 8.2 nm且形狀良好一致並無聚集情形，為增加生物相容性以及水溶性，修飾上生物相容性之高分子聚合物後，以 20MHz relaxometer測量其橫向弛緩率，其橫向弛緩率為 293 ± 5 mM-1s-1相較於市售之對比劑 Resovist TM之弛緩率 (164 mM-1s-1)高出許多，為了使其能做為多功能之影響探針使將超順磁氧化鐵-錳奈米粒子與近紅外光染料 Cy-TE777做結合，使之除了能做為 MRI對比劑外，亦能做為光學影像之探針。將已接合近紅外光染料 Cy-TE777之超順磁氧化鐵-錳奈米粒子與雙專一性之抗體接合，做為專一性之標靶探針，並以測量其橫向弛緩率得 199±5 mM-1s-1，仍高於市售對比劑 ResovistTM之橫向弛緩率，預期能獲得較佳之顯影效果。根據體外細胞實驗結果，本研究所合成之雙專一性氧化鐵-錳奈米粒子之細胞毒性低，同時具有標靶之目的癌細胞之功能性，不僅可減少對正常細胞之毒殺性，亦可做為極具發展潛力之癌細胞檢測探針。

Magnetic resonance imaging (MRI) is the best noninvasive technique in clinical diagnosis. However, MRI is not so sensitive like fluorescence imaging and nuclear medicine. To overcome this problem, iron oxide nanoparticles are used as contrast agent for MRI enhancement at tissue, cellular and molecular levels. Magnetic resonance (MR) tracking of superparamagnetic iron oxide (SPIO)-labeled cells is a relatively new technique to non-invasively determine the cancer cells. Tumor-targeted drug delivery can enhance the effectiveness of therapy while decreasing the systemic toxicity of these drugs. In this study, superparamagnetic iron oxide (SPIO) nanoparticles were synthesized by thermal decomposition. In order to get higher T2 relexivity, manganese doped iron oxide nanoparticles (MnFe2O4) were synthesized as the same way. The surface of MnFe2O4 were modified with mPEG-NH2-silane and conjugated with bispecific antibody to improve their dispersion, magnetization and ability to target specific receptors of cells. From the results, we found that the SPIO-Cy-TE777-Ab had well-dispersed in water , no hysteresis and high saturation magnetization (83.3emu/g).