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

JOURNAL OF CONTROLLED RELEASE

卷:174

Article

Tagalakis, Aristides D.¹  Kenny, Gavin D.¹  Bienemann, Alison S.²  McCarthy, David³  Munye, Mustafa M.¹  Taylor, Hannah²  Wyatt, Marcella J.²  Lythgoe, Mark F.^4,5  White, Edward A.²  Hart, Stephen L.¹ 

[1] UCL, Inst Child Hlth, Wolfson Ctr Gene Therapy Childhood Dis, London WC1N 1EH, England

[2] Univ Bristol, Southmead Hosp, Sch Clin Sci, AMBI Labs,Funct Neurosurg Res Grp, Bristol BS10 5NB, Avon, England

[3] UCL, Sch Pharm, London WC1N 1AX, England

[4] UCL, Ctr Adv Biol Imaging, Div Med, London WC1E 6DD, England

[5] UCL, Inst Child Hlth, London WC1E 6DD, England

关键词: Gene therapy;    Targeted;    Anionic;    Nanoparticle;    MRI;    Self-assembling;   

DOI  :  10.1016/j.jconrel.2013.11.014

来源: Elsevier

【 摘 要 】

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, nonspecific binding to cells, interaction with serum proteins and cell adhesion molecules and can lead to inflammatory responses. Anionic for mulations 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. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved.

【 授权许可】

Free