Complexation of well-controlled low-molecular weight polyelectrolytes with antisense oligonucleotides
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The influences of polymer-related properties such as molecular weight, charge density, counter ion, and hydrophilic block on the complexation of polyelectrolytes and a fluorescein-labeled oligonucleotide (ON) were investigated. A series of well-defined and well-controlled 2-(N,N-dimethylamino)ethyl methacrylate (DMAEMA) polymers and block copolymers were prepared using living anionic and radical polymerization methods. Fluorescence measurement was used to reveal the effects of polymer molecular weight, charge density, and counter ion type on the complexation. PolyDMAEMA samples having double molecular weights of the chosen oligonucleotide gave the optimal complexation performance. Kinetic studies showed that high-molecular weight/high-charge density polymer samples produced very stable complexes. The fully charged polyDMAEMA displayed the strongest binding with the ON. These complexes were therefore less sensitive to the changes in the environment. PolyDMAEMA–DMSQ samples had slightly higher complexation ability than polyDMAEMA–MCQ (DMSQ: dimethylsulfate quat; MCQ: methylchloride quat). Both poly(DMAEMA-b-HEMA) and poly(DMAEMA–MCQ-b-PEG) block copolymers showed good complexation ability and steric stability [HEMA: 2-hydroxyethyl methacrylate; PEG: poly(ethylene glycol)]. PEG, but not HEMA block, enhanced the effectiveness of polyDMAEMA–MCQ binding with the ON.
KeywordsPolyelectrolytes Complexation Antisense oligonucleotides Polymer vector Delivery Living polymerization
We would like to thank the Natural Science and Engineering Research Council of Canada (NSERC) and Canadian Foundation for Innovation (CFI) for the financial supports to both SZ and YL. We also thank Prof. S.P. Armes University of Sussex, UK for donating the PolyDMAEMA–MCQ and PolyDMAEMA–MCQ-b-PEO samples. JJ and JA would like to express their appreciations to the Ontario Ministry of Education and NSERC, respectively, for an OGS scholarship and an NSERC PGS A scholarship.
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