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• W2046365330 endingPage "2309" @default.
• W2046365330 startingPage "2301" @default.
• W2046365330 abstract "A series of diblock copolymers containing an endosomal-releasing segment composed of diethylaminoethyl methacrylate (DEAEMA) and butyl methacrylate (BMA) were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The materials were designed to condense plasmid DNA (pDNA) through electrostatic interactions with a cationic poly(N,N-dimethylaminoethyl methacrylate) (DMAEMA) first block. The pDMAEMA was employed as a macro chain transfer agent (macroCTA) for the synthesis of a series in which the relative feed ratios of DEAEMA and BMA were systematically varied from 20% to 70% BMA. The resultant diblock copolymers exhibited low polydispersity (PDI ≤ 1.06) with similar molecular weights (M(n) = 19.3-23.1 kDa). Dynamic light scattering (DLS) measurements in combination with (1)H NMR D(2)O studies demonstrated that the free copolymers assemble into core-shell micelles at physiological pH. Reduction of the solution pH to values representative of endosomal/lysosomal compartments induced an increase in the net cationic charge of the core through protonation of the DEAEMA residues. This protonation promotes micelle destabilization and exposure of the hydrophobic BMA residues that destabilize biological membranes. The pH value at which this micelle-to-unimer transition occurred was dependent on the hydrophobic content of the copolymer, with higher BMA-containing copolymer compositions exhibiting pH-induced transitions to the membrane-destabilizing state at successively lower pH values. The ability of the diblock copolymers to deliver pDNA was subsequently investigated using a GFP expression vector in two monocyte cell lines. High levels of DNA transfection were observed for the copolymer compositions exhibiting the sharpest pH transitions and membrane destabilizing activities, demonstrating the importance of tuning the endosomal-releasing segment composition." @default.
• W2046365330 created "2016-06-24" @default.
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• W2046365330 date "2012-03-01" @default.
• W2046365330 modified "2023-10-16" @default.
• W2046365330 title "Diblock copolymers with tunable pH transitions for gene delivery" @default.
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• W2046365330 doi "https://doi.org/10.1016/j.biomaterials.2011.11.019" @default.
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