Fabrication of Contrast Agents for Magnetic Resonance Imaging from Polymer-Brush-Afforded Iron Oxide Magnetic Nanoparticles Prepared by Surface-Initiated Living Radical Polymerization
Fabrication of Contrast Agents for Magnetic Resonance Imaging from Polymer-Brush-Afforded Iron Oxide Magnetic Nanoparticles Prepared by Surface-Initiated Living Radical Polymerization
复制标题
DOI：
10.1021/bm400770n
复制
发表时间：
2013-10-01
影响因子：
6.2
通讯作者：
Tabata, Yasuhiko
中科院分区：
文献类型：
--
作者：
Ohno, Kohji;Mori, Chizuru;Tabata, Yasuhiko
本研究的目的是通过使用由表面引发（SI）活性自由基聚合合成的由氧化铁磁铁矿（Fe 3 O 4）纳米颗粒的核和亲水性聚合物刷的壳组成的杂化颗粒来制备用于磁共振成像（MRI）的造影剂。为了实现这一点，Fe 3 O 4纳米粒子的表面改性与原子转移自由基聚合（ATRP）通过配体交换反应的存在下，具有ATRP引发位点的三乙氧基硅烷衍生物的引发基团。ATRP引发剂官能化的Fe 3 O 4纳米粒子用于进行甲基丙烯酸甲酯的SI-ATRP，以证明合成的纳米粒子在其表面上产生明确的聚合物刷的能力。聚合以活性方式进行，从而产生具有目标分子量和窄分子量分布的接枝聚合物。平均接枝密度估计高达0.7链/nm（2），这表明在Fe 3 O 4纳米颗粒上形成了所谓的浓缩聚合物刷。动态光散射和透射电子显微镜观察的混合纳米粒子显示其均匀性和溶解在溶剂中是优秀的。使用亲水性单体聚（乙二醇）甲基醚甲基丙烯酸酯（PEGMA）进行类似的聚合过程，以制备接枝有聚（PEGMA）刷的Fe 3 O 4纳米颗粒。所得的杂化纳米颗粒在包括生理条件的水性介质中显示出优异的分散性，而不引起任何聚集。通过静脉注射放射性同位素I-125标记的粒子到小鼠体内，研究了混合粒子的血液清除率和生物分布。发现一些杂化颗粒表现出极好的延长的血液循环寿命，半衰期约为24小时。当将这种杂交颗粒静脉注射到荷瘤小鼠中时，由于所谓的增强的渗透性和保留效应，它们优先在肿瘤组织中积累。通过T-2增强的MRI测量可视化肿瘤靶向递送。
The aim of this study is to fabricate a contrast agent for magnetic resonance imaging (MRI) by using hybrid particles composed of a core of iron oxide magnetite (Fe3O4) nanoparticles and a shell of hydrophilic polymer brush synthesized by surface-initiated (SI) living radical polymerization. To achieve this, Fe3O4 nanoparticles were surface-modified with initiating groups for atom transfer radical polymerization (ATRP) via a ligand-exchange reaction in the presence of a triethoxysilane derivative having an ATRP initiation site. The ATRP-initiator-functionalized Fe3O4 nanoparticles were used for performing the SI-ATRP of methyl methacrylate to demonstrate the ability of the synthesized nanoparticles to produce well-defined polymer brushes on their surfaces. The polymerization proceeded in a living fashion so as to produce graft polymers with targeted molecular weights and narrow molecular weight distribution. The average graft density was estimated to be as high as 0.7 chains/nm(2), which indicates the formation of so-called concentrated polymer brushes on the Fe3O4 nanoparticles. Dynamic light scattering and transmission electron microscope observations of the hybrid nanoparticles revealed their uniformity and dispersibility in solvents to be excellent. A similar polymerization process was conducted using a hydrophilic monomer, poly(ethylene glycol) methyl ether methacrylate (PEGMA), to prepare Fe3O4 nanoparticles grafted with poly(PEGMA) brushes. The resultant hybrid nanoparticles showed excellent dispersibility in aqueous media including physiological conditions without causing any aggregations. The blood clearance and biodistribution of the hybrid particles were investigated by intravenously injecting particles labeled with a radio isotope, I-125, into mice. It was found that some hybrid particles exhibited an excellently prolonged circulation lifetime in the blood with a half-life of about 24 h. When such hybrid particles were injected intravenously into a tumor-bearing mouse, they preferentially accumulated in the tumor tissues owing to the so-called enhanced permeability and retention effect. The tumor-targeted delivery was visualized by a T-2-enhaced MRI measurement.