Surface modification of crosslinked dextran nanoparticles influences transfection efficiency of dextran-polyethylenimine nanocomposites

Dextran-PEI grafted nanoparticles as transfection agents have been reported, however, with limited success due to their large size, poor buffering capacity and inadequate availability of charge for competent binding to DNA. To address these concerns, dextran was first crosslinked with 1,4-butanediol diglycidyl ether (BDE), a commercially available homobifunctional crosslinker, to form its nanoparticles (DN), which were then partially oxidized with sodium periodate to generate aldehyde functionalities on them. The resultant nanoparticles were grafted with branched polyethylenimine (bPEI, 25 kDa) to obtain a series of DN-PEI nanocomposites (DP), having comparatively smaller size, enhanced buffering capacity and competent binding ability with DNA. Subsequent to biophysical characterization, these nanocomposites were evaluated for their transfection efficiency in serum and serum-free environments and toxicity in various mammalian cell lines. A significantly (p < 0.05) improved transfection efficiency of these nanocomposites concurrent with their minimal cytotoxicity as compared to the selected commercial transfection agents and native PEI was observed. These results were further validated by intracellular trafficking, wherein DP4 (the best working system in the series) was able to carry the DNA inside the nucleus after 1 h of the addition of the complex. The in vivo gene expression profile of the DP4/DNA complex in male Balb/c mice exhibited maximum expression in their spleen tissue raising promise of using these nanocomposites as improved non-viral transfection agents.