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- W1988697693 abstract "Amphiphilic dimethylaminopyridinium alkyl polymethacrylates (aPPs) were tested for gene complexation, cell cytotoxicity and in vitro gene expression for use as gene delivery agents. The aminopyridinium groups neutralized by bromide or octylsulfonate counterions were terminal moieties of side-chain spacers containing 8, 12 or 16 methylene units. This investigation measured the impact of the spacer length and the chemical nature of the counterion on the physicochemical properties and biological activity of the polyplexes formed by the complexation with DNA. The aPPs self-assembled with DNA by neutralizing the DNA phosphate charges through the pyridinium moieties. The degree of DNA condensation was higher for shorter spacer (n = 8, 12) and bromide-neutralized aPPs. Several aPP–DNA complexes formed well-defined nanoparticles, which were usually, but not always, positively charged. Their sizes ranged from 30 to 150 nm and in some cases had an internal lamellar structure visible by TEM. All of the aPPs were found to be much less cytotoxic than branched poly(ethyleneimine) [(PEI), 25 kDa]. The degree of cytotoxicity of the aPPs depended mildly on their spacer length and counterion: a longer spacer (n = 16) decreased the cell viability more than shorter spacers and, at the highest aPP concentrations tested, bromide counterions more than octylsulfonate counterions. The transfection efficiency also depended on the spacer length and counterion type. Polyplexes obtained from the bromide-neutralized aPPs with the n = 12 spacer at an aPP/DNA weight ratio of 2.5, for which negatively charged nanoparticles were formed, were found to be as efficient as PEI-based polyplexes. Interestingly, this demonstrates that endosomolytic fragments and positively charged polyplex surfaces are not required for efficient gene expression." @default.
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- W1988697693 date "2009-01-01" @default.
- W1988697693 modified "2023-10-10" @default.
- W1988697693 title "Tail-end amphiphilic dimethylaminopyridinium-containing polymethacrylates for gene delivery" @default.
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- W1988697693 doi "https://doi.org/10.1039/b908419c" @default.
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