Division of Drug Delivery and Tissue Engineering, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK.
J Control Release. 2012 Mar 28;158(3):479-86. doi: 10.1016/j.jconrel.2011.12.009. Epub 2011 Dec 20.
In a study directed towards non-invasive delivery of therapeutic biomacromolecules, we examined whether surface modification of sub-200 nm model nanoparticles with the Fc portion of IgG promotes their cell uptake and transport across the airway epithelial cells. The study initially confirms the expression of the relevant receptor, namely neonatal Fc receptor (FcRn), by Calu-3 cell layers simulating the airway epithelium and demonstrates FcRn-mediated cell association, internalization and transcellular transport of molecular IgG. Surface decoration of nanoparticles with the Fc portion of IgG enhanced both cell uptake and translocation of the particulate system across the cell layers, in a manner strongly suggesting FcRn involvement in these processes. The study further demonstrates the potential of Fc-modified nanoparticles to 'shuttle' a model therapeutic antibody fragment across the epithelial cell layers. Fc-modified nanoparticles are transported in the μg/h/cm(2) range, presenting a substantial increase in transport capacity in comparison to molecular IgG (ng/h/cm(2) range), therefore warranting consideration of the FcRn transcytotic pathway for further investigation as a means to achieve transmucosal delivery of nanoparticulate systems that could act as carriers of a range of biotherapeutics.
在一项针对治疗性生物大分子非侵入性传递的研究中，我们研究了用 IgG 的 Fc 部分对亚 200nm 模型纳米颗粒进行表面修饰是否能促进其被气道上皮细胞摄取和转运。该研究最初证实了模拟气道上皮的 Calu-3 细胞层表达了相关受体，即新生 Fc 受体（FcRn），并证明了 FcRn 介导的分子 IgG 的细胞结合、内化和细胞间转运。用 IgG 的 Fc 部分对纳米颗粒进行表面修饰，能显著增强颗粒系统穿过细胞层的摄取和易位，强烈提示 FcRn 参与了这些过程。该研究进一步证明了 Fc 修饰的纳米颗粒有潜力“穿梭”穿过上皮细胞层传递模型治疗性抗体片段。Fc 修饰的纳米颗粒的转运量在μg/h/cm(2)范围内，与分子 IgG（ng/h/cm(2)范围）相比，转运能力有显著提高，因此有理由考虑 FcRn 转胞运输途径作为实现纳米颗粒系统跨粘膜传递的一种手段，这些纳米颗粒系统可以作为多种生物治疗药物的载体。
