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

A glutathione-sensitive cross-linked polyethylenimine gene vector CLPEI50% was specially designed via the cross-linking reaction between the low molecular weight polyethylenimine (PEI1800) and dimethyl 3.3'-dithiopropionimidate dihydrochloride (DTBP). The acid-base titration test indicated that CLPEI50% still possessed efficient proton sponge effect. The property of CLPEI50%-DNA complexes were investigated by atomic force microscopy (AFM) and dynamic light scattering (DLS). CLPEI50% 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 CLPEI50%-DNA polyplexes prepared at NIP ratio of 10 were unpacked at GSH concentration of 3 mm, which was comparable to the intracellular environment. The in vitro cytotoxicity of CLPEI50% was also significantly reduced comparing with PEI25k. The biomimetic CLPEI50%-DNA polyplexes with the low cytotoxicity and GSH-sensitive property could be a good candidate for gene delivery. (c) 2006 Elsevier Ltd. All rights reserved.