title: Impact of the nature, size and chain topologies of carbohydrate-phosphorylcholine polymeric gene delivery systems.
abstract: With the recent significant advances in the field polymer chemistry, it is now possible to produce well-defined and non-toxic cationic polymers with advanced molecular structures of desired molecular weights and compositions. Carefully engineered polymer architectures are found to impact significantly their DNA condensation and gene delivery efficacies. In a previous study, the statistical carbohydrates based copolymers were found to show high gene expression and low toxicity, however there aggregation in the presence of serum proteins was a major drawback. In this study, carbohydrate and phosphorylcholine based cationic polymers having a different architecture, compositions and varying molecular weights are produced and are termed as cationic 'block-statistical' copolymers. These cationic copolymers are evaluated for their gene delivery efficacies, interactions with serum protein, cellular uptake and nuclear localization ability. As compared to the statistical analogue, 'block-statistical' copolymers showed high gene expression, low interactions with serum proteins, as well as low toxicity in hepatocytes and human dermal fibroblasts. In addition, 2- methacryloyloxyethyl phosphorylcholine (MPC) based 'block-statistical' copolymers and their sugar incorporated analogues were prepared and were found to serve as improved gene delivery vectors than their statistical analogues.
authors: Department of Chemical and Materials Engineering, Alberta Glycomics Centre, University of Alberta, Edmonton, AB, Canada.
authors: Marya
authors: M
authors: Ahmed
authors: Manraj
authors: M
authors: Jawanda
authors: Kazuhiko
authors: K
authors: Ishihara
authors: Ravin
authors: R
authors: Narain
mesh_terms: D002241:Carbohydrates / Q000737:chemistry*; D002412:Cations; D002850:Chromatography, Gel; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018014:Gene Transfer Techniques; D056945:Hep G2 Cells; D006801:Humans; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D008970:Molecular Weight; D010316:Particle Size; D010767:Phosphorylcholine / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D012542:Scattering, Radiation; D014162:Transfection
chemical_list: D002241:Carbohydrates; D002412:Cations; D011108:Polymers; D010767:Phosphorylcholine