title: Bioreducible PEI-functionalized glycol chitosan: A novel gene vector with reduced cytotoxicity and improved transfection efficiency.
abstract: Non-viral gene delivery has been well recognised as a potential way to address the main safety limitations of viral gene carriers. A new redox-responsive PEI derivative was designed, synthesized and evaluated for non-viral delivery applications of GFP DNA. Glycol chitosan was covalently attached to highly branched LMW PEI via bio-cleavable disulfide bonds to synthesize a new redox-responsive gene carrier (GCS-ss-PEI). Results showed the enhanced buffering capacity of GCS-ss-PEI, 43.1%, compared to the buffering capacities of both LMW PEI and HMW PEI, 23.2% and 31.5%, respectively, indicating more likely endosomal escape of the entrapped gene for GCS-ss-PEI. Moreover, electrophoretic gel retardation assay, performed to investigate the binding strength of GCS-ss-PEI to GFP DNA, showed stronger complexation with GFP DNA in GCS-ss-PEI at non-GSH condition. Employing GCS and incorporation of disulfide bonds in the structure of the PEI-based gene carrier resulted in improved redox-responsivity, reduced toxicity, enhanced endosomal escape and GFP DNA transfection. The facilitated intracellular gene release along with excellent redox-responsive characteristics and dropped cytotoxicity suggests the potential of GCS-ss-PEI as a candidate for developing highly efficient and safe gene vectors.
authors: Department of Chemical Engineering, Faculty of Engineering, Monash University, Melbourne, VIC 3800, Australia; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Shahrouz
authors: S
authors: Taranejoo
authors: Department of Chemical Engineering, Faculty of Engineering, Monash University, Melbourne, VIC 3800, Australia.
authors: Ramya
authors: R
authors: Chandrasekaran
authors: Department of Chemical Engineering, Faculty of Engineering, Monash University, Melbourne, VIC 3800, Australia.
authors: Wenlong
authors: W
authors: Cheng
authors: Laboratory for Biomedical Engineering/Fluids Laboratory for Aeronautical and Industrial Research, Department of Mechanical and Aerospace Engineering, Faculty of Engineering, Monash University, Melbourne, VIC 3800, Australia. Electronic address: Kerry.hourigan@monash.edu.
authors: Kerry
authors: K
authors: Hourigan
mesh_terms: D048271:Chitosan / Q000737:chemistry*; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004220:Disulfides / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D010084:Oxidation-Reduction; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry; D014162:Transfection / Q000379:methods*
chemical_list: D004220:Disulfides; C118638:glycol-chitosan; D049452:Green Fluorescent Proteins; D011094:Polyethyleneimine; D004247:DNA; D048271:Chitosan
keywords: Cytotoxicity; GCS-ss-PEI; Glycol chitosan; Non-viral vector; PEI; Redox-responsive