title: Rational design of biodegradable cationic polycarbonates for gene delivery.
abstract: 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.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Zhan Yuin
authors.initials: ZY
authors.lastname: Ong
authors.forename: Kazuki
authors.initials: K
authors.lastname: Fukushima
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Coady
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: D002412:Cations / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D011076:Polycarboxylate Cement / Q000737:chemistry*
chemical_list: D002412:Cations; D011076:Polycarboxylate Cement; C005506:polycarbonate; D004247:DNA