Interdisciplinary Nanoscience Center (iNANO), Departments of Molecular Biology and Genetics, Physics and Astronomy, Aarhus University, DK-8000 Aarhus C, Denmark.
Nanoscale. 2013 Sep 7;5(17):8192-201. doi: 10.1039/c3nr32922d.
Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery.
超顺磁性氧化铁（USPIO）纳米颗粒目前被用作体内磁共振成像（MRI）的对比剂，主要通过其在感兴趣的组织中的被动积累。然而，当纳米颗粒靶向细胞特异性受体时，可以实现更高的特异性，并且这也可能通过增强的靶向介导内吞作用促进特定的药物传递。我们报告了将磁性纳米颗粒高效地靶向表达尿激酶纤溶酶原激活物受体（uPAR）的细胞，uPAR 是包括乳腺癌、结直肠癌和胃癌在内的几种癌症的预后不良的表面生物标志物。通过点击化学将 uPAR 特异性靶向肽缀合到聚乙二醇（PEG）涂覆的 USPIO 纳米颗粒上，与携带非结合对照肽的纳米颗粒相比，在 uPAR 阳性细胞系中体外摄取增加了五倍。与特异性受体介导的识别一致，在存在过量 ATF（uPAR 的天然配体）的情况下，观察到摄取较低。当与 MRI 和药物递送结合使用时，uPAR 特异性磁性纳米颗粒可能为肿瘤患者管理提供有用的补充。
