Uptake and transfection efficiency of PEGylated cationic liposome-DNA complexes with and without RGD-tagging.

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Bibtex

@article{3cc9d9a78d984cb091a95b5f77661b63,
title = "Uptake and transfection efficiency of PEGylated cationic liposome-DNA complexes with and without RGD-tagging.",
abstract = "Steric stabilization of cationic liposome-DNA (CL-DNA) complexes is required for in vivo applications such as gene therapy. PEGylation (PEG: poly(ethylene glycol)) of CL-DNA complexes by addition of PEG2000-lipids yields sterically stabilized nanoparticles but strongly reduces their gene delivery efficacy. PEGylation-induced weakening of the electrostatic binding of CL-DNA nanoparticles to cells (leading to reduced uptake) has been considered as a possible cause, but experimental results have been ambiguous. Using quantitative live-cell imaging in vitro, we have investigated cell attachment and uptake of PEGylated CL-DNA nanoparticles with and without a custom synthesized RGD-peptide grafted to the distal ends of PEG2000-lipids. The RGD-tagged nanoparticles exhibit strongly increased cellular attachment as well as uptake compared to nanoparticles without grafted peptide. Transfection efficiency of RGD-tagged PEGylated CL-DNA NPs increases by about an order of magnitude between NPs with low and high membrane charge density (σM; the average charge per unit area of the membrane; controlled by the molar ratio of cationic to neutral lipid), even though imaging data show that uptake of RGD-tagged particles is only slightly enhanced by high σM. This suggests that endosomal escape and, as a result, transfection efficiency of RGD-tagged NPs is facilitated by high σM. We present a model describing the interactions between PEGylated CL-DNA nanoparticles and the anionic cell membrane which shows how the PEG grafting density and membrane charge density affect adhesion of nanoparticles to the cell surface.",
author = "Majzoub, {Ramsey N} and Chia-Ling Chan and Ewert, {Kai K} and Bruno Silva and Liang, {Keng S} and Jacovetty, {Erica L} and Bridget Carragher and Potter, {Clinton S} and Safinya, {Cyrus R}",
year = "2014",
doi = "10.1016/j.biomaterials.2014.03.007",
language = "English",
volume = "35",
pages = "4996--5005",
journal = "Biomaterials",
issn = "1878-5905",
publisher = "Elsevier",
number = "18",

}