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The biggest challenge in the field of gene therapy is how to effectivelydeliver target genes to special cells. This study aimed to develop a new type ofPLGA-based nanoparticles for gene delivery, which are capable of overcoming thedisadvantages of PEI or cationic liposome based gene carrier, such as the cytotoxicityinduced by excess positive charge, as well as the aggregation on the cell surface. ThePLGA-based nanoparticles presented in this study were synthesized by emulsionevaporation method and characterized by transmission electron microscopy (TEM),dynamic light scattering (DLS) and Energy dispersive spectroscopic (EDS). The sizeof PLGA/PEI nanoparticles in PBS was about 60 nm at the optimal charge ratio.Without observable aggregation, the nanoparticles showed a better monodispersity.The PLGA-based nanoparticles were used as vector carrier for miRNA transfection inHepG2 cells. It exhibited a higher transfection efficiency and lower cytotoxicity inHepG2 cells compared to the PEI/DNA complex. The N/P ratio (ratio of the polymernitrogen to the DNA phosphate) 6 of the PLGA/PEI/DNA nanocomplex displays thebest property among various N/P proportions, yielding similar transfection efficiencywhen compared to Lipofectamine/DNA lipoplexes. Moreover, nanocomplex showsbetter serum compatibility than commercial liposome. PLGA nanocoplexes obviouslyaccumulate in tumor cells after transfection, which indicate that the complexcontribute to cellular uptake of pDNA, and pronouncedly enhance the treatment effectof miR-26a by inducing cell cycle arrest. Therefore, these results demonstrate thatPLGA/PEI nanoparticles are promising non-viral vectors for gene delivery.