Fluorescence Imaging with Multifunctional Polyglycerol Sulfates: Novel Polymeric near-IR Probes Targeting Inflammation
Fluorescence Imaging with Multifunctional Polyglycerol Sulfates: Novel Polymeric near-IR Probes Targeting Inflammation
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DOI：
10.1021/bc2002727
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发表时间：
2011-12-01
影响因子：
4.7
通讯作者：
Schirner, Michael
中科院分区：
文献类型：
--
作者：
Licha, Kai;Welker, Pia;Schirner, Michael
我们提出了一种高度选择性的方法，用于用多价聚合物探针靶向炎症。用树枝状聚甘油与吲哚青绿(ICG)相关的近红外荧光染料合成了一种聚阴离子大分子偶联物。在多元醇核生成的硫酸盐基团密集聚集的基础上，得到的聚甘油硫酸酯(分子量12kD，类似于70个硫酸盐基团)靶向炎症因子(IC50值为3-6 nM，用于抑制L-选择素的结合)，并特异性地转运到炎症细胞中。在类风湿关节炎动物模型中，近红外荧光成像研究的体内蓄积显示出快速和选择性的摄取，这使得能够区分病变关节(评分1-3)，荧光水平高3.5倍，信号在注射后60分钟达到最大值。荧光组织学定位显示，结合物沉积在滑膜的炎性浸润液中，而非硫酸盐对照与疾病无关。因此，这种类型的聚合物成像探针是当前生物结合物的替代，并为靶向成像和药物输送提供了未来的选择。
We present a highly selective approach for the targeting of inflammation with a multivalent polymeric probe. Dendritic polyglycerol was employed to synthesize a polyanionic macromolecular conjugate with a near-infrared fluorescent dye related to Indocyanine Green (ICG). On the basis of the dense assembly of sulfate groups which were generated from the polyol core, the resulting polyglycerol sulfate (molecular weight 12 kD with similar to 70 sulfate groups) targets factors of inflammation (IC50, of 3-6 nM for inhibition of L-selectin binding) and is specifically transported into inflammatory cells. The in vivo accumulation studied by near-IR fluorescence imaging in an animal model of rheumatoid arthritis demonstrated fast and selective uptake which enabled the differentiation of diseased joints (score 1-3) with a 3.5-fold higher fluorescence level and a signal maximum at 60 min post injection. Localization in tissues using fluorescence histology showed that the conjugates are deposited in the inflammatory infiltrate in the synovial membrane, whereas nonsulfated control was not detected in association with disease. Hence, this type of polymeric imaging probe is an alternative to current bioconjugates and provides future options for targeted imaging and drug delivery.