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Novel Biodegradable Block Copolymers of Poly(ethylene glycol) (PEG) and Cationic Polycarbonate: Effects of PEG Configuration on Gene Delivery
Author(s) -
Yang Chuan,
Ong Zhan Yuin,
Yang YiYan,
Ee Pui Lai Rachel,
Hedrick James L.
Publication year - 2011
Publication title -
macromolecular rapid communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.348
H-Index - 154
eISSN - 1521-3927
pISSN - 1022-1336
DOI - 10.1002/marc.201100350
Subject(s) - cationic polymerization , polycarbonate , ethylene glycol , copolymer , peg ratio , gene delivery , polymer chemistry , materials science , living cationic polymerization , polymer , pegylation , zeta potential , ring opening polymerization , chemistry , polyethylene glycol , organic chemistry , transfection , nanotechnology , nanoparticle , biochemistry , finance , economics , gene
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.