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.