N-isopropylacrylamide-modified polyethylenimines as effective gene carriers.

25 kDa branched polyethylenimines are modified by N-isopropylacrylamide via Michael addition. An agarose gel retardation assay shows that all derivatives display good binding affinity toward plasmid DNA. The modified PEI-25K shows lower cytotoxicity in MTT assay and better transfection efficiency than unmodified PEI-25K in HeLa cells. The endocytosis efficiency of the optimized complexes is determined to be 99.9% by flow cytometry. More interestingly, although the derivatives are not designed to conjugate with targeting ligands or nuclear localization signals, confocal laser scanning microscopy (CLSM) demonstrates that the optimized derivative results in increased endocytosis and strongly enhanced nuclear uptake compared with PEI-25K.