PURPOSE: A novel core-shell gene delivery system was fabricated in order to improve its gene transfection efficiency, particularly in the presence of serum. MATERIALS AND METHODS: alpha, beta-poly (L-aspartate-graft-PEI) (PAE) was simply synthesized by ring-opening reaction of poly (L-succinimide) with low molecular weight (LMW) linear polyethylenimine (PEI, Mn = 423). PAE/DNA nanoparticles were characterized. Condensation and protection ability of plasmid by PAE were confirmed by agarose gel electrophoresis assay. Cytotoxicity of the polymer and polymer/DNA nanoparticles were measured by MTS assay. Gene transfection efficiencies were evaluated both in vitro and in vivo. RESULTS: Core-shell nanoparticles assembled between DNA and PAE showed positive zeta potential, narrow size distribution, and spherical compact shapes with size below 250 nm when N/P ratio is above 10. Cytotoxicity of PAE was rather lower than that of PEI 25K, while the most efficient gene transfection and serum resistant ability of PAE/DNA complexes were higher than that of PEI 25K. Bafilomycin A1 treatment suggested "proton sponge" mechanism of PAE-mediated gene transfection. PAE/pEGFP-N2 nanoparticles also showed good gene expression in vivo and were dominantly distributed in kidney, liver, spleen and lung after intravenous administration. CONCLUSIONS: The results demonstrated the potential use of PAE as an effective gene carrier.
PURPOSE: A novel core-shell gene delivery system was fabricated in order to improve its gene transfection efficiency, particularly in the presence of serum. MATERIALS AND METHODS:alpha, beta-poly (L-aspartate-graft-PEI) (PAE) was simply synthesized by ring-opening reaction of poly (L-succinimide) with low molecular weight (LMW) linear polyethylenimine (PEI, Mn = 423). PAE/DNA nanoparticles were characterized. Condensation and protection ability of plasmid by PAE were confirmed by agarose gel electrophoresis assay. Cytotoxicity of the polymer and polymer/DNA nanoparticles were measured by MTS assay. Gene transfection efficiencies were evaluated both in vitro and in vivo. RESULTS: Core-shell nanoparticles assembled between DNA and PAE showed positive zeta potential, narrow size distribution, and spherical compact shapes with size below 250 nm when N/P ratio is above 10. Cytotoxicity of PAE was rather lower than that of PEI 25K, while the most efficient gene transfection and serum resistant ability of PAE/DNA complexes were higher than that of PEI 25K. Bafilomycin A1 treatment suggested "proton sponge" mechanism of PAE-mediated gene transfection. PAE/pEGFP-N2 nanoparticles also showed good gene expression in vivo and were dominantly distributed in kidney, liver, spleen and lung after intravenous administration. CONCLUSIONS: The results demonstrated the potential use of PAE as an effective gene carrier.
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