Targeting of polyamidoamine-DNA nanoparticles using the Staudinger ligation: attachment of an RGD motif either before or after complexation.
Two new methods for the modular synthesis of targeted gene delivery systems are reported. The PEGylated polyamidoamine DMEDA-PEG-DMEDA-(MBA-DMEDA)(n+1)-PEG-DMEDA 3 was sequentially modified to contain an integrin-binding peptide ligand via the Staudinger ligation. The conjugation of the ligand was achieved either before particle complexation (precomplexation) or after particle complexation (postcomplexation). Comparison of the two systems showed that postcomplexation strategy led to small and discrete toroidal nanoparticles whilst the precomplexation particles showed loose complexes. The targeted particles showed an increased uptake into cells compared to unmodified complexes however no significant increase in transfection was seen.
Parkhouse
Susan M
SM
School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Garnett
Martin C
MC
Chan
Weng C
WC
D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009842:Oligopeptides / Q000737:chemistry*; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry*
D009842:Oligopeptides; D011073:Polyamines; C047981:arginyl-glycyl-aspartic acid; D004247:DNA