Targeting of cancer cells with ferrimagnetic ferritin cage nanoparticles
Targeting of cancer cells with ferrimagnetic ferritin cage nanoparticles
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DOI：
10.1021/ja0655690
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发表时间：
2006-12-27
影响因子：
15
通讯作者：
Douglas, Trevor
中科院分区：
文献类型：
--
作者：
Uchida, Masaki;Flenniken, Michelle L.;Douglas, Trevor
蛋白质笼结构，如病毒衣壳和铁蛋白是通用的纳米级平台，适合遗传和化学修饰。这些纳米尺寸的蛋白质结构中的多个功能的结合展示了它们作为功能性纳米材料在医学成像和治疗中的应用的潜力。在本研究中，我们合成了一个氧化铁（磁铁矿）纳米粒子内的基因工程人类H-链铁蛋白（HFn）的内腔。将细胞特异性靶向肽RGD-4C基因整合到HFn的外表面上，所述细胞特异性靶向肽RGD-4C结合在肿瘤脉管系统上上调的α（v）β（3）整联蛋白。含磁铁矿和荧光标记的RGD 4C-Fn笼在体外结合C32黑色素瘤细胞。这些结果共同证明了遗传修饰的蛋白质笼结构作为多功能纳米级容器用于同时负载氧化铁和细胞特异性靶向的能力。
Protein cage architectures such as virus capsids and ferritins are versatile nanoscale platforms amenable to both genetic and chemical modification. Incorporation of multiple functionalities within these nanometer-sized protein architectures demonstrate their potential to serve as functional nanomaterials with applications in medical imaging and therapy. In the present study, we synthesized an iron oxide (magnetite) nanoparticle within the interior cavity of a genetically engineered human H-chain ferritin (HFn). A cell-specific targeting peptide, RGD-4C which binds alpha(v)beta(3) integrins upregulated on tumor vasculature, was genetically incorporated on the exterior surface of HFn. Both magnetite-containing and fluorescently labeled RGD4C-Fn cages bound C32 melanoma cells in vitro. Together these results demonstrate the capability of a genetically modified protein cage architecture to serve as a multifunctional nanoscale container for simultaneous iron oxide loading and cell-specific targeting.