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

Aristides Tagalakis, G Kenny, A.S. Bienemann, D McCarthy, M.M. Munye, H Taylor, M.J. Wyatt, M.F. Lyhtgoe, E.A. White, S.L. Hart

Research output: Contribution to journalArticle

36 Citations (Scopus)
72 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)177-187
Number of pages11
JournalJournal of Controlled Release
Volume174
Issue number1
Early online date22 Nov 2013
DOIs
Publication statusPublished - 28 Jan 2014

Keywords

  • Anionic
  • Gene therapy
  • MRI
  • Nanoparticle
  • Self-assembling
  • Targeted

Fingerprint Dive into the research topics of 'PEGylation improves the receptor-mediated transfection efficiency of peptide-targeted, self-assembling, anionic nanocomplexes'. Together they form a unique fingerprint.

  • Profiles

    No photo of ARISTIDES TAGALAKIS

    Dr ARISTIDES TAGALAKIS

    Person: Member, Academic

    Cite this

    Tagalakis, A., Kenny, G., Bienemann, A. S., McCarthy, D., Munye, M. M., Taylor, H., Wyatt, M. J., Lyhtgoe, M. F., White, E. A., & Hart, S. L. (2014). PEGylation improves the receptor-mediated transfection efficiency of peptide-targeted, self-assembling, anionic nanocomplexes. Journal of Controlled Release, 174(1), 177-187. https://doi.org/10.1016/j.jconrel.2013.11.014