Biodegradable and versatile polyethylenimine derivatives efficiently transfer DNA and siRNA into mammalian cells.

UNLABELLED: Polyethylenimines (PEIs) are considered as the most promising vectors for non-viral gene delivery applications. Here, we report the synthesis and in vitro evaluation of two non-toxic and biodegradable polymers, TEPA@bPEI (TBP) and TEPA@lPEI (TLP), derived from low molecular weight branched and linear polyethylenimines by the stepwise reactions with methylacrylate (aza-Michael reaction) and amidation with tetraethylenepentamine (TEPA). These polymers not only showed their ability to bind and condense pDNA into nano-sized complexes but also provided protection against nucleases in cellular milieu. Both the polymers exhibited excellent buffering capacity and efficiently delivered nucleic acids (plasmid DNA and siRNA) across the mammalian cells (CHO and A549 cells) and outclassed native polymers and the commercial transfection reagents in terms of transfection efficiency and target gene silencing, and that too without compromising on biocompatibility i.e. TOXICITY: The results advocate the promising potential of the PEI derivatives as safe and potent nucleic acid carriers for practical gene delivery applications.