Abstract
Cationic polymers are known to afford efficient gene transfection. However, cytotoxicity remains a problem at the molecular weight for optimal DNA delivery. As such, optimized polymeric gene delivery systems are still a sought-after research goal. A guanidinylated bioreducible branched polyethylenimine (GBPEI-SS) was synthesized by using a disulfide bond to crosslink the guanidinylated BPEI (GBPEI). GBPEI-SS showed sufficient plasmid DNA (pDNA) condensation ability. The physicochemical properties of GBPEI-SS demonstrate that it has the appropriate size (~200 nm) and surface potential (~30 mV) at a nitrogen-to-phosphorus ratio of 10. No significant toxicity was observed, possibly due to bioreducibility and to the guanidine group delocalizing the positive charge of the primary amine in BPEI. Compared with the nonguanidinylated analogue, BPEI-SS, GBPEI-SS showed enhanced transfection efficiency owing to increased cellular uptake and efficient pDNA release by cleavage of disulfide bonds. This system is very efficient for delivering pDNA into cells, thereby achieving high transfection efficiency and low cytotoxicity.
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