A highly efficient siRNA carrier of PBLG modified hyperbranched PEI

In search for effective non-viral gene vectors for the delivery of siRNA, a copolymer was designed and synthesized by grafting hydrophobic poly(γ-benzyl L-glutamate) segment (PBLG) to hyperbranched polyethylenimine (PEI-PBLG). PEI-PBLG could efficiently deliver siRNA to cells to silence the targeted gene. Markedly, PEI-PBLG caused lower cytotoxicity in comparison to unmodified PEI. The siRNA complexed with PEI-PBLG showed a remarkable knockdown (75.23% relative to untreated cells, without changing the medium after 6 h of incubation) of the targeted luciferase gene in stable expressing luciferase CT26 cells while the Lipofectamine ™2000 and unmodified PEI could only achieve knockdown rates of 57.92% and 15.31%, respectively. The siRNA complexed with PEI-PBLG also demonstrated that it had greater gene silencing ability than unmodified PEI and Lipofectamin™2000 in both 4T1 cells stably transfected with the luciferase gene and HeLa cells transiently transfected with the luciferase gene. The internalization efficiency of carrier/ Alexa647-labeled siRNA was quantified using flow cytometry. PEI-PBLG/Alexa647-labeled siRNA showed internalization efficiency of 52.67% while PEI and Lipofectamine™2000 demonstrated 27.23% and 37.91%, respectively. Confocal laser scanning microscopy (CLSM) assay also indicated that PEIPBLG induced higher cell uptake efficiency than other commercial reagents. PEI-PBLG was shown to be a promising siRNA carrier with potential application in cancer therapy.