A mannosylated cell-penetrating peptide-graft-polyethylenimine as a gene delivery vector
2014
Abstract Polyethylenimine (PEI) is widely applied in non-viral gene delivery vectors. PEI with high molecular weight is highly effective in gene transfection but is high cytotoxic. Conversely, PEI with low molecular weight displays lower cytotoxicity but less delivering efficiency. To overcome this issue, a novel copolymer with mannosylated, a cell-penetrating peptide (CPP), grafting into PEI with molecular weight of 1800 (Man-PEI 1800 -CPP) were prepared in this study to target antigen-presenting cells (APCs) with mannose receptors and enhance transfection efficiency with grafting CPP. The copolymer was characterized by 1 H NMR and FTIR. Spherical nanoparticles were formed with diameters of about 80–250 nm by mixing the copolymer and DNA at various charge ratios of copolymer/DNA(N/P). Gel retardation assays indicated that Man-PEI 1800 -CPP polymers efficiently condensed DNA at low N/P ratios. Cytotoxicity studies showed that Man-PEI 1800 -CPP/DNA complexes maintained in a high percentage of cell viability compared to the PEI with molecular weight of 25 k (PEI 25k ). Laser scan confocal microscopy and flow cytometry confirmed that Man-PEI 1800 -CPP/DNA complexes resulted in higher cell uptake efficiency on DC2.4 cells than on Hela cells line. The transfection efficiency of Man-PEI 1800 -CPP was significantly higher than that of PEI 25k on DC2.4 cells. More importantly, the complexes were mainly distributed in the epidermis and dermis of skin and targeted on splenocytes after percutaneous coating based on microneedles in vivo. These results indicated that Man-PEI 1800 -CPP was a potential APCs targeted of non-virus vector for gene therapy.
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