Synthesis and Characterization of the Specific Superparamagnetic Iron Oxide Nanoparticles MnMEIO-silane-NH2-mPEG for Magnetic Resonance Imaging

• Main Authors: Wu, Shou-Cheng, 吳首成
• Other Authors: Wang, Yun-Ming
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/39142761291098095448

博士 === 國立交通大學 === 生物科技系所 === 102 === A new multifunctional nanoparticles (MnMEIO-silane-NH2-mPEG NPs), consisting of a manganese-doped iron oxide nanoparticle core (MnMEIO), a copolymer shell of silane and amine-functionalized poly(ethylene glycol), were successfully developed in this study for improving the solubility and biocompatibility of the contrast agent. There are two key features in MnMEIO-silane-NH2-mPEG, one is -NH2 functional group between silane and mPEG which can be used as a binding site for bio-probes and NIRF dyes result in the MR-optical dual modalities of nanoparticles. The other is the flexible PEG, which masks the non-conjugated reactive amine groups (-NH2 + H+  -NH3+) and reduces nonspecific binding of MnMEIO-silane-NH2-mPEG to cells. The nanoparticles (MnMEIO-silane-NH2-mPEG) are provided with the properties of water solubility and superparamagnetism in this study. The relaxivities (r1 and r2) of the MnMEIO-silane-NH2-mPEG NPs measured at 20 MHz and 37.0 ± 0.1 °C were 42.1 ± 1.7 and 293.5 ± 6.2 mM-1s-1, respectively. This indicates that the nanoparticles can efficiently improve the imaging contrast. Furthermore, the DLS data indicate no significant variation in hydrodynamic size of MnMEIO-silane-NH2-mPEG NPs across a wide pH range (pH 4-10), reassuring high colloidal stability of MnMEIO-silane-NH2-mPEG NPs under physiological conditions. Finally, no significant variation in hydrodynamic size and relaxivity of MnMEIO-silane-NH2-mPEG NPs were observed over a long time period. The in vitro and in vivo results experimentally demonstrated that the anti-EGFR antibody conjugated nanoparticles (MnMEIO-silane-NH2-(Erb)-mPEG NPs) could significantly reduce nonspecific binding and increase the imaging specificity to EGFR-overexpressing tumors. Besides, the anti-mucin4 antibody (MUC4) were used to forming the nanoparticles (MnMEIO-silane-NH2-(MUC4)-mPEG NPs) for diagnosis of mucin4-expressing pancreatic tumors. Besed on the results, MnMEIO-silane-NH2-mPEG NPs is a well-established platform to combine different targeting moieties for diagnostic and therapeutic use of various tumors. Furthermore, a multifunctional nanoparticles (MnMEIO-silane-NH2-(Bis)-mPEG NPs) which covalently conjugated anti-Her2/neu and anti-EGFR receptors bispecific antibody (Bis) were also developed for recognizing the tumors expressing both Her2/neu and/or EGFR. For Her2/neu-overexpressing tumors, MnMEIO-silane-NH2-(Bis)-mPEG can be a potential targeting agent for Herceptin replacement. For the current tumor diagnosis associated studies, this study which applied bispecific antibosies as a targeting moiety is the first approach in tumoral diagnosis area. These experimental results demonstrated that nanoparticles conjugated with various monoclonal antibody could specifically and effectively target to tumors. As a results, a MR-optical dual modality contrast agent system with high biocompatibility and stability is performed for the design and development of the next-generation nanoscale diagnostic and therapeutic modalities.