Dextran–spermine polycation: an efficient nonviral vector for in vitro and in vivo gene transfection

Abstract

Dextran-spermine cationic polysaccharide was prepared by means of reductive amination between oxidized dextran and the natural oligoamine spermine. The formed Schiff-base imine-based conjugate was reduced with borohydride to obtain the stable amine-based conjugate. The transfection efficiency of the synthetic dextran-spermine was assessed in vitro on HEK293 and NIH3T3 cell lines and found to be as high as the DOTAP/Chol 1/1 lipid-based transfection reagent. Modification of the dextran-spermine polycation with polyethylene glycol resulted in high transfection yield in serum-rich medium. Intramuscular injection in mice of dextran-spermine-pSV-LacZ complex induced high local gene expression compared to low expression of the naked DNA. Intravenous injection of a dispersion of the dextranspermine-pSV-LacZ complex resulted with no expression in all examined organs. When the partially PEGylated dextranspermine-pSV-LacZ complex was intravenously applied, a high gene expression was detected mainly in the liver. Preliminary targeting studies indicated that the PEGylated dextran-spermine-pSV-LacZ complex bound to galactose receptor of liver parenchymal cells rather than the mannose receptor of liver nonparenchymal cells. This work offers a new biodegradable polycation based on natural components, which is capable of transfecting cells and tissues in vitro and in vivo.

Development of 3D in vitro platform technology to engineer mesenchymal stem cells

“…17 Incorporation of plasmid DNA into dextran-spermine was performed by simply mixing two materials at various charge ratios (N/P, indicated as the molar ratio of the spermine nitrogen of dextran-spermine to the phosphate molecules of plasmid DNA) in aqueous solution. Briefly, 150 µL of 0.1 M phosphate-buffered saline solution (PBS, pH 7.4) containing 2.5, 5, 10, 25, and 100 µg of dextran-spermine was added to the same volume of PBS containing 10 µg of plasmid DNA.…”

“…We have reported that the dextran-spermine based polycations have been found to be highly effective as nonviral vectors in transfecting many different cells in vitro. [11][12][13][14][15][16][17] Our recent study also demonstrated that electrospun poly (glycolic acid) (PGA)/ collagen nanofibers significantly enhanced cell adhesion compared with PGA/collagen microfibers. 18 Based on these results, the present study aims to fabricate a tissue-like 3D transgene cell construct for use as a therapeutic cell-based gene delivery system or as an in vitro model system for testing genetic manipulations to understand the effects of gene expression on tissue development.…”

RETRACTED ARTICLE: Enhanced suppression of tumor growth using a combination of NK4 plasmid DNA-PEG engrafted cationized dextran complex and ultrasound irradiation

“…[39][40][41] Our previous study demonstrated that dextran significantly enhanced in vitro and in vivo gene trasnfection. 42 To give the dextran a cationized charge, which is necessary for the formation of polyion complexes with plasmid DNA, spermine was introduced to the hydroxyl groups of dextran. The cationized dextran was then reacted with poly(ethylene glycol) (PEG) and mixed with NK4 plasmid DNA in aqueous solution.…”

Synthesis and characterization of novel water-soluble polyamide based on spermine and aspartic acid as a potential gene delivery vehicle

“…The incorporation of PEG in gene vectors in various creative capacities is a widely used strategy for improving the polyplex solubility and reduce polyplex aggregation and prolong the circulation time [2,5,7,12,28,48]. Both spermine and aspartic acid, being natural materials are biodegradable and its copolymer with an aliphatic amide bonding is expected to be also biodegradable [50].…”