Diaminododecane-based cationic bolaamphiphile as a non-viral gene delivery carrier

Majad Khan, Chung Yen Ang, Nikken Wiradharma, Lin Kin Yong, Shaoqiong Liu, Lihong Liu, Shujun Gao, Yi Yan Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

The advancement in gene therapy relies upon the discovery of safe and efficient delivery agents and methods In this study, we report the design and synthesis of a cationic bolaamphiphile as a non-viral gene delivery agent The bolaamphiphile is composed of 1,12-diaminododecane as the central hydrophobic unit linked to the hydrophilic pentaethylenehexamine via thioether-based glycidyl units This bolaamphiphile condensed DNA efficiently into nanoparticles of sizes around 150-200 nm with positive zeta potential of 30-35 mV In vitro luciferase expression levels and percentage of GFP expressing cells induced by the bolaamphiphile/DNA complexes were higher than those mediated by the often used " golden" standard of non-viral systems, polyethyleneimine (PEI, branched, 25 kDa) at its optimal N/P ratio in HEK293, HepG2, NIH3T3, HeLa and 4T1 cells In vitro cytotoxicity testing revealed that the DNA complexes fabricated from this cationic bolaamphiphile displayed marginal toxicity towards all the cell lines tested In addition, in vivo transfection studies carried out in a 4T1 mouse breast cancer model showed that the cationic bolaamphiphile delivered DNA more efficiently than PEI This cationic bolaamphiphile may make a promising gene delivery vector for future gene therapy.

Original languageEnglish
Pages (from-to)4673-4680
Number of pages8
JournalBiomaterials
Volume33
Issue number18
DOIs
StatePublished - Jun 2012
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to thank Miss Siti Nurhanna Riduan (IBN, Singapore) for her help in NMR experiments. Also financial support from Institute of Bioengineering and Nanotechnology (Biomedical Research Council, Agency for Science, Technology and Research, Singapore) is gratefully acknowledged.

Keywords

  • Bolaamphiphile
  • Cationic
  • GFP gene
  • Gene delivery
  • In vivo gene transfection
  • Luciferase gene

ASJC Scopus subject areas

  • Mechanics of Materials
  • Ceramics and Composites
  • Bioengineering
  • Biophysics
  • Biomaterials

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