The development and characterization of a glutathione-sensitive cross-linked polyethylenimine gene vector

A glutathione-sensitive cross-linked polyethylenimine gene vector CLPEI(50%) was specially designed via the cross-linking reaction between the low molecular weight polyethylenimine (PEI(1800)) and dimethyl 3.3'-dithiopropionimidate dihydrochloride (DTBP). The acid-base titration test indicated that CLPEI(50%) still possessed efficient proton sponge effect. The property of CLPEI(50%)-DNA complexes were investigated by atomic force microscopy (AFM) and dynamic light scattering (DLS). CLPEI(50%) induced DNA condensation and formed spherical nanoparticles. The diameter of polyplexes prepared at pH value of 6.0 and 7.4 was about 150 and 260 nm, respectively. It was interesting to find the polyplexes were sensitive to the reductive glutathione (GSH). The CLPEI(50%)-DNA polyplexes prepared at N/P ratio of 10 were unpacked at GSH concentration of 3mm, which was comparable to the intracellular environment. The in vitro cytotoxicity of CLPEI(50%) was also significantly reduced comparing with PEI(25k). The biomimetic CLPEI(50%)-DNA polyplexes with the low cytotoxicity and GSH-sensitive property could be a good candidate for gene delivery.