利用 LPPC 包覆超順磁氧化鐵-錳奈米粒子及 doxorubicin 用於診斷與治療

Abstract

本研究中用Liposomes containing polyethylenimine and polyethylene glycol（LPPC）微脂體包覆本實驗室所開發的水溶性超順磁氧化鐵-錳奈米粒子（MnMEIO-NH2），以 20 MHz relaxometer測量其橫向弛緩率，其橫向弛緩率為 270.6 ± 6.7 mM-1s-1相較於市售之對比劑ResovistTM之弛緩率（162.6 ± 0.8 mM-1s-1）高出許多，為了使其能做為多功能之影像探針，並包覆近紅外光染料Cy-TE777（Cy777），使之除了能做為 MRI對比劑外，亦能做為光學影像之探針。近紅外光螢光染料，可同時應用於光學與磁振造影（MRI），並測量其橫向弛緩率得269.7 ± 4.3 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。並接上抗體Erbitux（Erb），使LPPC-Cy777-MnMEIO-Erb具有標靶性，以達到特異性標定的目的，使其有更高量的積聚於腫瘤，將LPPC-Cy777-MnMEIO-Erb，包覆抗癌藥物（doxorubicin）其平均包覆率為24.9%。

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. Novel aspect of nanotechnology and biotechnology has been extensively exploited to develop multimodal contrast agent for cancer detection. Liposomes containing polyethylenimine and polyethylene glycol (LPPC) can provide a platform to capture biologically and biochemically functional proteins on its surface for various applications. In this study, we developed highly specific dual modality T2 weighted MR-optical imaging agents (LPPC-Cy777-MnMEIO-Erb) for targeting moiety to target EGFR receptor which is exclusively expressed in cancer. The LPPC-Cy777-MnMEIO-Erb consist of MnMEIO-NH2 and CyTE777 as MR enhancer and NIR dye respectively. The r2 relaxivity values of the LPPC-Cy777-MnMEIO-NH2 measured at 20 MHz and 37.0 ± 0.1 C are 269.7 ± 4.3 mM-1s-1.We use LPPC-Cy777-MnMEIO-Erb to encapsulation the drug (doxorubicin),which can enhance the effectiveness of therapy while decreasing the systemic toxicity of these drugs.