TY - JOUR
T1 - Bioreducible PEI-functionalized glycol chitosan
T2 - A novel gene vector with reduced cytotoxicity and improved transfection efficiency
AU - Taranejoo, Shahrouz
AU - Chandrasekaran, Ramya
AU - Cheng, Wenlong
AU - Hourigan, Kerry
PY - 2016
Y1 - 2016
N2 - 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 bufferingcapacities 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 disulfidebonds 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 ofGCS-ss-PEI as a candidate for developing highly efficient and safe gene vectors.
AB - 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 bufferingcapacities 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 disulfidebonds 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 ofGCS-ss-PEI as a candidate for developing highly efficient and safe gene vectors.
KW - GCS-ss-PEI
KW - Glycol chitosan
KW - PEI
KW - Redox-responsive
KW - Non-viral vector
KW - Cytotoxicity
UR - https://www-scopus-com.ezproxy.lib.monash.edu.au/record/display.uri?eid=2-s2.0-84979515554&origin=resultslist&sort=plf-f&src=s&st1=Bioreducible+PEI-functionalized+glycol+chitosan&st2=&sid=6509F16C3813EC5F7723E672D8E6700F.CnvicAmOODVwpVrjSeqQ%3a340&sot=b&sdt=b&sl=62&s=TITLE-ABS-KEY%28Bioreducible+PEI-functionalized+glycol+chitosan%29&relpos=0&citeCnt=0&searchTerm=
U2 - 10.1016/j.carbpol.2016.07.080
DO - 10.1016/j.carbpol.2016.07.080
M3 - Article
SN - 0144-8617
VL - 153
SP - 160
EP - 168
JO - Carbohydrate Polymers
JF - Carbohydrate Polymers
ER -