Combined targeting of lentiviral vectors and positioning of transduced cells by magnetic nanoparticles
Combined targeting of lentiviral vectors and positioning of transduced cells by magnetic nanoparticles
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DOI：
10.1073/pnas.0803746106
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发表时间：
2009-01-06
影响因子：
11.1
通讯作者：
Pfeifer, Alexander
中科院分区：
文献类型：
--
作者：
Hofmann, Andreas;Wenzel, Daniela;Pfeifer, Alexander
靶向病毒载体是体内基因递送的主要挑战，特别是在血管内应用之后。此外，靶向内皮细胞本身对于血管疾病的基因治疗将是重要的。在这里，我们使用磁性纳米粒子（MNP）结合联合收割机细胞转导和定位在血管系统中的临床相关的，不允许的条件下，包括流体动力学和低温。MNP的使用增强了内皮细胞的转导效率，并通过磁力实现了慢病毒载体（LV）的直接内皮靶向，甚至在灌注的血管中。此外，对小鼠施加外部磁场显著改变了LV/MNP在体内的生物分布。LV/MNP转导的细胞表现出超顺磁性行为，通过磁弛豫法测量，并且它们被磁场有效地保留。在生理流动条件下，磁相互作用足够强以将含MNP的内皮细胞定位在血管内膜处。重要的是，磁性定位的MNP标记的细胞也实现了在体内的小鼠颈动脉损伤模型。血管内基因靶向可以与通过纳米磁性颗粒定位转导的细胞相结合，从而结合基于基因和细胞的治疗。
Targeting of viral vectors is a major challenge for in vivo gene delivery, especially after intravascular application. In addition, targeting of the endothelium itself would be of importance for gene-based therapies of vascular disease. Here, we used magnetic nanoparticles (MNPs) to combine cell transduction and positioning in the vascular system under clinically relevant, nonpermissive conditions, including hydrodynamic forces and hypothermia. The use of MNPs enhanced transduction efficiency of endothelial cells and enabled direct endothelial targeting of lentiviral vectors (LVs) by magnetic force, even in perfused vessels. In addition, application of external magnetic fields to mice significantly changed LV/MNP biodistribution in vivo. LV/MNP-transduced cells exhibited superparamagnetic behavior as measured by magnetorelaxometry, and they were efficiently retained by magnetic fields. The magnetic interactions were strong enough to position MNP-containing endothelial cells at the intima of vessels under physiological flow conditions. Importantly, magnetic positioning of MNP-labeled cells was also achieved in vivo in an injury model of the mouse carotid artery. Intravascular gene targeting can be combined with positioning of the transduced cells via nanomagnetic particles, thereby combining gene- and cell-based therapies.