Research On Glucocorticoid-PEI As A Novel Gene Delivery System

In this research,five different but similar Glucocorticoids(GC) were conjugated onto low molecular weight polyethylenimine(PEI 1800) by a two-step reaction by using the Traut's reagent.Our purpose was to create a kind of low cytotoxic and highly efficient gene delivery system which could complex with pDNA to form compact nanoparticles and efficiently translocate into the nucleus.The GC-PEIs/pDNA complexes were prepared and their physico-chemical properties were investigated.The results showed that the complexes had similar physicochemical properties.The experiments of cytotoxicity and transfection efficiency of the GC-PEIs were also checked in cultured HEK 293 cell line and HepG2 cell line.The results showed that their cytotoxicity were lower than PEI 25k. Furthermore,DEX-PEI/pDNA and BET-PEI/pDNA polyplexes had similar or even greater gene delivery efficiency compared to PEI 25k/pDNA complex.The results of confocal microscopy examination and in vivo experiments on ICR mice confirmed these findings.In order to study the relationships between the structure of GC substitute and transfection activity mediated by GC-PEIs,we performed molecular docking program to check the docking and binding energy between GC and GR.Furthermore,we compared two method used to analyze the relationships—by potency or LogP,and conclude that potency could be a potential index to indicate the transfection effects.