The role of cytoskeleton networks on lipid-mediated delivery of DNA. (February 2013)

• Record Type: Journal Article
• Authors: Coppola, Stefano; Cardarelli, Francesco; Pozzi, Daniela; Estrada, Laura C; Digman, Michelle A; Gratton, Enrico; Bifone, Angelo; Marianecci, Carlotta; Caracciolo, Giulio
• Is Part Of: Therapeutic delivery. Volume 4:Number 2(2013)
• Page Start: 191
• Page End: 202
• Publication Date: 2013-02
• Subjects: Drug delivery systems -- Periodicals; Therapeutics -- Periodicals; 615.6
• DOI: 10.4155/tde.12.151
• Languages: English
• ISSNs: 2041-5990

Abstract

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.