Department of Nanomedicine, The Methodist Hospital System Research Institute, Houston, Texas 77030, USA.
Nat Nanotechnol. 2013 Jan;8(1):61-8. doi: 10.1038/nnano.2012.212. Epub 2012 Dec 16.
The therapeutic efficacy of systemic drug-delivery vehicles depends on their ability to evade the immune system, cross the biological barriers of the body and localize at target tissues. White blood cells of the immune system--known as leukocytes--possess all of these properties and exert their targeting ability through cellular membrane interactions. Here, we show that nanoporous silicon particles can successfully perform all these actions when they are coated with cellular membranes purified from leukocytes. These hybrid particles, called leukolike vectors, can avoid being cleared by the immune system. Furthermore, they can communicate with endothelial cells through receptor-ligand interactions, and transport and release a payload across an inflamed reconstructed endothelium. Moreover, leukolike vectors retained their functions when injected in vivo, showing enhanced circulation time and improved accumulation in a tumour.
系统药物输送载体的治疗效果取决于其逃避免疫系统、穿过身体的生物屏障并定位于目标组织的能力。免疫系统的白细胞具有所有这些特性,并通过细胞膜相互作用发挥其靶向能力。在这里,我们表明,当纳米多孔硅粒子被包裹在从白细胞中提取的细胞膜时,它们可以成功地完成所有这些操作。这些混合粒子,称为类白细胞载体,可以避免被免疫系统清除。此外,它们可以通过受体-配体相互作用与内皮细胞进行通信,并在发炎的重建内皮细胞中运输和释放有效载荷。此外,类白细胞载体在体内注射时保留了其功能,表现出更长的循环时间和在肿瘤中的更好积累。