Bioreducible PEI-functionalized glycol chitosan

A novel gene vector with reduced cytotoxicity and improved transfection efficiency

Shahrouz Taranejoo, Ramya Chandrasekaran, Wenlong Cheng, Kerry Hourigan

Research output: Contribution to journalArticleResearchpeer-review

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 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.
Original languageEnglish
Pages (from-to)160-168
Number of pages9
JournalCarbohydrate Polymers
Volume153
DOIs
Publication statusPublished - 2016

Keywords

  • GCS-ss-PEI
  • Glycol chitosan
  • PEI
  • Redox-responsive
  • Non-viral vector
  • Cytotoxicity

Cite this

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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 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.",
keywords = "GCS-ss-PEI, Glycol chitosan, PEI, Redox-responsive, Non-viral vector, Cytotoxicity",
author = "Shahrouz Taranejoo and Ramya Chandrasekaran and Wenlong Cheng and Kerry Hourigan",
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journal = "Carbohydrate Polymers",
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Bioreducible PEI-functionalized glycol chitosan : A novel gene vector with reduced cytotoxicity and improved transfection efficiency. / Taranejoo, Shahrouz; Chandrasekaran, Ramya; Cheng, Wenlong; Hourigan, Kerry.

In: Carbohydrate Polymers, Vol. 153, 2016, p. 160-168.

Research output: Contribution to journalArticleResearchpeer-review

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.

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M3 - Article

VL - 153

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JO - Carbohydrate Polymers

JF - Carbohydrate Polymers

SN - 0144-8617

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