Correction for 'Efficient gene transfection to liver cells via the cellular regulation of a multifunctional polylactitol-based gene transporter' by Young-Dong Kim et al., J. Mater. Chem. B, 2016, 4, 2208-2218.
Vectors are vital aspect of gene delivery system which decides the success of gene therapy. Efficient transfection with minimum or no toxicity, are two principal aims of any gene delivery system. In this our study, we rationally developed biodegradable water soluble poly(ßamino ester) (PAE) based on spermine (SPR) and poly (ethylene glycol) (PEG), by Michael-type addition reaction and further studied for its potential as a gene carrier. Confirmation of synthesized PAE was done by proton NMR spectroscopy. In gel retardation assay, the PAEs have shown good DNA binding ability over wide range of polyplexes. The addition of PEG over SPR resulted in a novel PAE with higher degree of safety and transfection efficiency as compared with polyethylenimine 25K (PEI) when studied in 293T human kidney carcinoma cells.
Polyethylenimine (PEI) vectors are widely used in gene delivery because of their high transfection efficiency owing to a unique proton sponge effect. An increase in molecular weight increases transfection efficiency, but simultaneously results in increased toxicity. Therefore, the design and synthesis of new degradable gene delivery carriers having high transfection efficiencies and reduced cytotoxicity are necessary.In the present study degradable poly(ester amines) (PEAs) based on glycerol dimethacrylate (GDM) and low molecular weight branched polyethylenimine (LMW-PEI) were synthesized in anhydrous methanol at 60 degrees C following Michael addition reaction. The transfection efficiencies of the synthesized PEA/DNA complexes were evaluated using three different cell lines (HeLa, HepG2 and 293T cells) in vitro.PEAs with zeta potential in the range of 30-55 mV (at physiological pH) condensed plasmid DNA into nanosized particles (<150 nm) suitable for intracellular delivery. The PEAs degraded in a controlled fashion (t(1/2) of approximately 9-10 days). Compared with PEI 25K, the PEAs showed significantly lower cytotoxicity in three different cells. The PEAs demonstrated much higher transfection efficiency compared to conventional PEI 25K and Lipofectamine. The PEA synthesized using a 1 : 4 mole ratio of GDM to PEI [GDM/PEI-1.2 (1:4)] showed the highest transfection efficiency in HepG2 cells. Significantly higher pEGFP-N(2) reporter gene expression in 293T cells was achieved using these PEAs. The hyperosmotic effect of PEAs was demonstrated by the reduction in packed cell volume (PCV). The GDM/PEI-1.2 (1:4) showed comparable reduction in PCV with respect to glycerol in 293T cells. The effect of bafilomycin A(1) on transfection efficiency of PEAs on 293T cells indicated its endosomal buffering capacity.We hypothesized that the higher transfection efficiency of PEAs was the synergistic effect arising from hyperosmotic glycerol and endosomal buffering capacity of PEAs resulting from the presence of a glycerol backbone and PEI amine groups, respectively.
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