A series of diblock copolymers containing an endosomal-releasing segment composed of diethylaminoethyl methacrylate (DEAEMA) and butyl methacrylate (BMA) at varying molar feed ratios and a plasmid DNA-condensing segment of dimethylaminoethyl methacrylate (DMAEMA) were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization.  These diblock copolymers self-assemble into micelles at physiological pH but undergo a phase transition at lower pH values.  The pH at which this transition occurs can be precisely tuned by modification of the BMA content.  Diblock copolymers with 30 � 40 % BMA content exhibited phase transitions at pH values similar to those encountered in the early and late endosomes.  These materials showed significant levels of red blood cell lysis at these pH values but negligible cell lysis under physiological conditions.  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.

Diblock copolymers with tunable pH transitions for gene delivery

243rd National Meeting (2012)

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