期刊
THERAPEUTIC DELIVERY
卷 4, 期 2, 页码 191-202出版社
FUTURE SCI LTD
DOI: 10.4155/TDE.12.151
关键词
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资金
- Italian Minister for University and Research (MIUR) (Futuro in Ricerca) [RBFR08TLPO]
- Italian Minister for University and Research (MIUR) (Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale) [2009ACFPN9_002]
- National Center for Research Resources [5P41RR003155]
- National Institute of General Medical Sciences divisions of the NIH [8P41GM103540, 5P50 GM076516]
Background: Lipid-mediated delivery of DNA is hindered by extracellular and intracellular barriers that significantly reduce the transfection efficiency of synthetic nonviral vectors. Results: In this study we investigated the role of the actin and microtubule networks on the uptake and cytoplasmic transport of multicomponent cationic liposome-DNA complexes in CHO-K1 live cells by means of confocal laser scanning microscopy and 3D single particle tracking. Treatment with actin (latrunculin B)- and microtubule-disrupting (nocodazole) reagents indicated that intracellular trafficking of complexes predominantly involves microtubule-dependent active transport. We found that the actin network has a major effect on the initial uptake of complexes, while the microtubule network is mainly responsible for the subsequent active transportation to the lysosomes. Conclusion: Collectively, a strategy to improve the efficiency of lipid gene vectors can be formulated. We could find a lipid formulation that allows the nanoparticles to avoid the microtubule pathway to lysosomes.
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