Optimization of Magnetic Nanoparticle-Assisted Lentiviral Gene Transfer
Optimization of Magnetic Nanoparticle-Assisted Lentiviral Gene Transfer
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DOI：
10.1007/s11095-011-0660-x
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发表时间：
2012-01
影响因子：
3.7
通讯作者：
Christina Trueck;Katrin Zimmermann;O. Mykhaylyk;M. Anton;Sarah Vosen;D. Wenzel;B. Fleischmann;A. Pfeifer
中科院分区：
文献类型：
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作者：
Christina Trueck;Katrin Zimmermann;O. Mykhaylyk;M. Anton;Sarah Vosen;D. Wenzel;B. Fleischmann;A. Pfeifer
目的靶向特异性细胞和组织是临床相关基因和细胞治疗的重要研究方向。我们使用具有铁磁核心（Fe3O4）的磁性纳米颗粒（MNPs），并采用不同的涂层来优化mnp辅助慢病毒基因转移，重点关注不同的内皮细胞系。方法采用不同的方法（如磁响应性测量）对slentiviral vector (LV)/MNP结合进行表征。通过流式细胞术、荧光显微镜和铁回收分析转导细胞。利用不同的vitroandex体内系统进行生理流动条件下的细胞转导和细胞定位。结果对不同涂层的MNPs进行分析，鉴定出具有改善LV关联和增强复合物转导特性的纳米颗粒。LV/MNP复合物的磁矩足够高，可以实现灌注内皮细胞的局部基因靶向。在临床相关的血流条件下，用LV/MNP转导的细胞灌注小鼠主动脉，导致血管内膜局部细胞附着。结论优化后的MNPs可显著增强内皮细胞的慢病毒转导。
PurposeTargeting of specific cells and tissues is of great interest for clinical relevant gene- and cell-based therapies. We use magnetic nanoparticles (MNPs) with a ferrimagnetic core (Fe3O4) with different coatings to optimize MNP-assisted lentiviral gene transfer with focus on different endothelial cell lines.MethodsLentiviral vector (LV)/MNP binding was characterized for various MNPs by different methods (e.g. magnetic responsiveness measurement). Transduced cells were analyzed by flow cytometry, fluorescence microscopy and iron recovery. Cell transduction and cell positioning under physiological flow conditions were performed using differentin vitroandex vivosystems.ResultsAnalysis of diverse MNPs with different coatings resulted in identification of nanoparticles with improved LV association and enhanced transduction properties of complexes in several endothelial cell lines. The magnetic moments of LV/MNP complexes are high enough to achieve local gene targeting of perfused endothelial cells. Perfusion of a mouse aorta with LV/MNP transduced cells under clinically relevant flow conditions led to local cell attachment at the intima of the vessel.ConclusionMNP-guided lentiviral transduction of endothelial cells can be significantly enhanced and localized by using optimized MNPs.