Low molecular weight PEI-based polycationic gene vectors via Michael addition polymerization with improved serum-tolerance

A series of polycationic gene delivery vectors were synthesized via Michael addition from low molecular weight PEI and linking compounds with various heteroatom compositions. Agarose gel electrophoresis results reveal that these polymers can well condense plasmid DNA and can protect DNA from degradation by nuclease. The formed polyplexes, which are stable toward serum, have uniform spherical nanoparticles with appropriate sizes around 200-350 nm and zeta-potentials about +40 mV. In vitro experiments show that these polymers have lower cytotoxicity and higher transfection efficiency than 25 KDa PEI. Furthermore, the title materials exhibit excellent serum tolerance. With the present of 10% serum, up to 19 times higher transfection efficiency than PEI was obtained, and no obvious decrease of TE was observed even the serum concentration was raised to >40%. Flow cytometry and confocal microscopy studies also demonstrate the good serum tolerance of the materials. (C) 2015 Elsevier Ltd. All rights reserved.