Thermally cross-linked superparamagnetic iron oxide nanoparticles: Synthesis and application as a dual Imaging probe for cancer in vivo
Thermally cross-linked superparamagnetic iron oxide nanoparticles: Synthesis and application as a dual Imaging probe for cancer in vivo
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DOI：
10.1021/ja072210i
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发表时间：
2007-10-24
影响因子：
15
通讯作者：
Jon, Sangyong
中科院分区：
文献类型：
--
作者：
Lee, Haerim;Yu, Mi Kyung;Jon, Sangyong
我们报道了热交联超顺磁性氧化铁纳米颗粒（TCL-SPION）的制备和表征及其在体内癌症双重成像中的应用。与通过化学交联方法制备的葡聚糖涂层交联氧化铁纳米颗粒不同，TCLSPION通过使用含Si-OH共聚物的简单热交联方法制备。采用自由基聚合法合成了聚（甲基丙烯酸3-（三甲氧基硅基）丙酯-r-聚乙二醇甲基醚甲基丙烯酸酯-r-N-丙烯酰氧基琥珀酰亚胺）共聚物，并将其用作合成磁铁矿（Fe 3 O 4）SPION的包覆材料。将聚合物涂覆的SPION在80 ° C下进一步加热以诱导聚合物链中的-Si（OH）（3）基团之间的交联，这最终产生带有羧基作为表面官能团的TCL-SPION。的粒径，表面电荷，聚合物涂层的存在下，和热交联的程度进行了表征和确认的各种测量，包括动态光散射，傅立叶变换红外光谱，和X-射线光电子能谱。将羧基TCL-SPION转化为胺修饰的TCL-SPION，然后最终转化为Cy5.5染料缀合的TCL-SPION，用于双重（磁共振/光学）体内癌症成像。当通过静脉注射将Cy5.5 TCL-SPION给予刘易斯肺癌肿瘤同种异体移植小鼠时，在4小时内在T-2加权磁共振图像中以及在光学荧光图像中明确检测到肿瘤为68%的信号下降，表明肿瘤部位内纳米磁体的高水平积累。此外，收获的肿瘤和其他主要器官的离体荧光图像进一步证实了Cy5.5 TCL-SPION在肿瘤内的最高积累。值得注意的是，尽管事实上TCL-SPION在其表面上不携带任何靶向配体，但其通过双重成像用于体内肿瘤检测是高度有效的。
We report the fabrication and characterization of thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) and their application to the dual imaging of cancer in vivo. Unlike dextrancoated cross-linked iron oxide nanoparticles, which are prepared by a chemical cross-linking method, TCLSPION are prepared by a simple, thermal cross-linking method using a Si-OH-containing copolymer. The copolymer, poly(3-(trimethoxysilyl)propyl methacrylate-r-PEG methyl ether methacrylate-r-N-acryloxysuccinimide), was synthesized by radical polymerization and used as a coating material for as-synthesized magnetite (Fe3O4) SPION. The polymer-coated SPION was further heated at 80 degrees C to induce cross-linking between the -Si(OH)(3) groups in the polymer chains, which finally generated TCL-SPION bearing a carboxyl group as a surface functional group. The particle size, surface charge, presence of polymer-coating layers, and the extent of thermal cross-linking were characterized and confirmed by various measurements, including dynamic light scattering, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The carboxyl TCL-SPION was converted to amine-modified TCL-SPION and then finally to Cy5.5 dyeconjugated TCL-SPION for use in dual (magnetic resonance/optical) in vivo cancer imaging. When the Cy5.5 TCL-SPION was administered to Lewis lung carcinoma tumor allograft mice by intravenous injection, the tumor was unambiguously detected in T-2-weighted magnetic resonance images as a 68% signal drop as well as in optical fluorescence images within 4 h, indicating a high level of accumulation of the nanomagnets within the tumor site. In addition, ex vivo fluorescence images of the harvested tumor and other major organs further confirmed the highest accumulation of the Cy5.5 TCL-SPION within the tumor. It is noteworthy that, despite the fact that TCL-SPION does not bear any targeting ligands on its surface, it was highly effective for tumor detection in vivo by dual imaging.