<p> Cationic polyelectrolytes have attracted growing attention in the field of non-viral
oligonucleotides (ONs) deliveries because of their ability to bind ONs by electrostatic
interactions for efficient cellular uptake. However the formation of electrostatic
polymer/ONs complexes and their biological effects are still poorly understood. The
relationships between polymer structure and complexation performance have not been
well established. The objectives of this research are to synthesize and characterize well-defined and well-controlled cationic polyelectrolytes and to evaluate the effects of
polyelectrolyte chain properties on ONs complexation. Poly(2-(dimethylamino) ethyl
methacrylate) (polyDMAEMA) and its derivatives are used as the polymer candidate. A
fluorescein-labeled oligonucleotide, 5 '-FGCGGAGCGTGGCAGG-3' (F: fluorescein), is
used as the oligonucleotide candidate.</p> <p> Low-molecular-weight cationic polyDMAEMA samples having narrow molecular weight distribution were synthesized by living anionic polymerization (LAP) and atom transfer radical polymerization (ATRP) methods. Fully charged polyDMAEMA quats were prepared by sequential quaternization of polyDMAEMA samples, as well as by direct ATRP of the quaternized DMAEMA monomer. An aqueous GPC calibration
method was first developed for the characterization of these cationic polyelectrolytes. It
was found that the type of counter-ion has little effect on the hydrodynamic volume of
polyDMAEMA quat. Therefore the dimethyl sulfate salt of polyDMAEMA provided a
reliable calibration standard for other types of quaternized DMAEMA homopolymers.</p> <p> Cationic block copolymers of polyDMAEMA with 2-hydroxyethyl methacrylate
(HEMA) and polyethylene glycol (PEG) were also prepared by ATRP. It was found that
the order of monomer addition, solvent type, temperature, and molecular weight of
macroinitiator have significant effects on the living feature of the polymerization. Well-controlled block copolymers were obtained when polyHEMA was used as the macro initiator.</p> <p> The complexation capability of the prepared polyelectrolytes with
oligonucleotides (15 mer) was evaluated by a fluorescence technique. It was found that
the complexation performance depends on polymer molecular weight, charge density,
and counter-ion type, as well as polymer concentration and block composition. The
polymer sample that has double molecular weight of the ONs gave the optimal
complexation performance.</p> / Thesis / Master of Applied Science (MASc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/19388 |
| Date | 11 1900 |
| Creators | Jin, Xiaopin |
| Contributors | Zhu, Shiping, Chemical Engineering |
| Source Sets | McMaster University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
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