title: Novel biodegradable block copolymers of poly(ethylene glycol) (PEG) and cationic polycarbonate: effects of peg configuration on gene delivery.
abstract: A novel amine-functionalized polycarbonate was synthesized and its excellent gene transfection ability in vitro is demonstrated. In the framework of adapting the cationic polycarbonate for in vivo gene delivery applications, here the design and synthesis of biodegradable block copolymers of poly(ethylene glycol) (PEG) and amine-functionalized polycarbonate with a well-defined molecular architecture and molecular weight is achieved by metal-free organocatalytic ring-opening polymerization. Copolymers in triblock cationic polycarbonate-block-PEG-block-cationic polycarbonate and diblock PEG-block-cationic polycarbonate configurations, in comparison with a non-PEGylated cationic polycarbonate control, are investigated for their influence on key aspects of gene delivery. Among the polymers with similar molecular weights and N content, the triblock copolymer exhibit more favorable physicochemical (i.e., DNA binding, size, zeta-potential, and in vitro stability) and biological (i.e., cellular uptake and luciferase reporter gene expression) properties. Importantly, the various cationic polycarbonate/DNA complexes are biocompatible, inducing minimal cytotoxicities and hemolysis. These results suggest that the triblock copolymer is a more useful architecture in future cationic polymer designs for successful systemic therapeutic applications.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Chuan
authors.initials: C
authors.lastname: Yang
authors.forename: Zhan Yuin
authors.initials: ZY
authors.lastname: Ong
authors.forename: Yi-Yan
authors.initials: YY
authors.lastname: Yang
authors.forename: Pui Lai Rachel
authors.initials: PL
authors.lastname: Ee
authors.forename: James L
authors.initials: JL
authors.lastname: Hedrick
mesh_terms: D018014:Gene Transfer Techniques / Q000295:instrumentation*; D017930:Genes, Reporter; D056945:Hep G2 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D011076:Polycarboxylate Cement / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D011076:Polycarboxylate Cement; D011108:Polymers; C005506:polycarbonate; D011092:Polyethylene Glycols; D008156:Luciferases