title: Functional polycarbonates and their self-assemblies as promising non-viral vectors.
abstract: Polycarbonates are promising biomaterials due to their biocompatibility, degradability and low toxicity. In this study, a series of COOH-functionalized polycarbonates was synthesized via an organocatalytic ring opening polymerization pathway under mild conditions. The polymers displayed a range of molecular weights (M(w): 3.1, 5.5 and 9.7 kDa) and were very narrowly distributed (polydispersity index: 1.07, 1.07 and 1.15 respectively). Aliphatic amines with different chain lengths (triethylenetetramine, tetraethylenepentamine or pentaethylenehexamine) were then conjugated onto the polycarbonate backbone using DIC/NHS chemistry. These amine-functionalized polycarbonates could form nanoparticles upon simple dissolution in water and had CMC values ranging from 22 to 45 mg/L. It was found that a longer amine chain resulted in greater buffering capacity, more positive zeta potential and smaller hydrodynamic size of the polymeric nanoparticles. Results from gel retardation assays indicated that the polymers were able to condense DNA. In-vitro studies further demonstrated that selected amine-functionalized polycarbonates could mediate efficient luciferase expression in HEK293, HepG2 and 4T1 cell lines at levels that were comparable, or even superior, to the polyethylenimine (PEI) standard. Importantly, minimal cytotoxicty was induced in the cells. These functional polycarbonates therefore have the potential to be a useful non-viral vector for gene therapy.
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
authors.forename: Wei Yang
authors.initials: WY
authors.lastname: Seow
authors.forename: Yi Yan
authors.initials: YY
authors.lastname: Yang
mesh_terms: D002021:Buffers; D002152:Calorimetry, Differential Scanning; D002384:Catalysis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D004563:Electrochemistry; D005822:Genetic Vectors; D006865:Hydrogenation; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D010316:Particle Size; D011076:Polycarboxylate Cement / Q000138:chemical synthesis / Q000737:chemistry*; D012685:Sepharose / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013059:Spectrum Analysis, Raman; D013818:Thermogravimetry
chemical_list: D002021:Buffers; D007202:Indicators and Reagents; D008823:Micelles; D011076:Polycarboxylate Cement; C005506:polycarbonate; D012685:Sepharose