Rational design of biodegradable cationic polycarbonates for gene delivery

Polycarbonates provide an attractive option for use as gene delivery vectors owing to their biocompatibility and ease of incorporating functional moieties. In this study, we described an approach to synthesize cationic polymers with well-defined molecular weights and narrow polydispersities by an organocatalytic ring-opening polymerization of functional cyclic carbonates containing alkyl halide side chains, followed by a subsequent functionalization step with bis-tertiary amines designed to facilitate gene binding and endosomal escape. The cationic polycarbonate effectively condensed DNA at low N/P ratios, generating nanoparticles (83 to 124 nm in diameter) with positive zeta potentials (~ 27 mV). In addition, reporter gene expression efficiencies in HepG2, HEK293, MCF-7 and 4T1 cell lines were high even in the presence of serum. Importantly, the polycarbonate delivery agent demonstrated minimal cytotoxicity at the optimal N/P ratios determined to confer high gene expression efficiencies. Therefore, this biodegradable polymer is presented as a promising non-viral vector for gene delivery.

Graphical AbstractNarrowly dispersed cationic polycarbonates were synthesized by living ring opening polymerization. The prototype biodegradable polymer condensed DNA efficiently and mediated high luciferase expression in various cell lines with minimal cytotoxicity.Figure optionsDownload as PowerPoint slide