PEGylation improves the receptor-mediated transfection efficiency of peptide-targeted, self-assembling, anionic nanocomplexes

Tagalakis, Aristides, Kenny, G, Bienemann, A.S., McCarthy, D, Munye, M.M., Taylor, H, Wyatt, M.J., Lyhtgoe, M.F., White, E.A. and Hart, S.L. (2014) PEGylation improves the receptor-mediated transfection efficiency of peptide-targeted, self-assembling, anionic nanocomplexes. Journal of Controlled Release, 174. pp. 177-187. ISSN 0168-3659 DOI i0.1016/j.jconrel.2013.11.014

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Abstract

Non-viral vector formulations comprise typically complexes of nucleic acids with cationic polymers or lipids. However, for in vivo applications cationic formulations suffer from problems of poor tissue penetration, non-specific binding to cells, interaction with serum proteins and cell adhesion molecules and can lead to inflammatory responses. Anionic formulations may provide a solution to these problems but they have not been developed to the same extent as cationic formulations due to difficulties of nucleic acid packaging and poor transfection efficiency. We have developed novel PEGylated, anionic nanocomplexes containing cationic targeting peptides that act as a bridge between PEGylated anionic liposomes and plasmid DNA. At optimized ratios, the components self-assemble into anionic nanocomplexes with a high packaging efficiency of plasmid DNA. Anionic PEGylated nanocomplexes were resistant to aggregation in serum and transfected cells with a far higher degree of receptor-targeted specificity than their homologous non-PEGylated anionic and cationic counterparts. Gadolinium-labeled, anionic nanoparticles, administered directly to the brain by convection-enhanced delivery displayed improved tissue penetration and dispersal as well as more widespread cellular transfection than cationic formulations. Anionic PEGylated nanocomplexes have widespread potential for in vivo gene therapy due to their targeted transfection efficiency and ability to penetrate tissues.

Item Type: Article
Uncontrolled Keywords: Anionic; Gene therapy; MRI; Nanoparticle; Self-assembling; Targeted
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Divisions: Biology
Date Deposited: 25 Apr 2018 13:55
URI: http://repository.edgehill.ac.uk/id/eprint/10266

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