Low molecular weight PEI-appended polyesters as non-viral gene delivery vectors

•Novel low molecular weight PEI-appended biodegradable polymers were prepared.•These polymers have much lower cytotoxicity than 25 kDa PEI in several cell lines.•The polyplex gave 54 times higher transfection efficiency than PEI/DNA complex.

Routine clinical implementation of human gene therapy requires safe and efficient gene delivery methods. Linear biodegradable polyesters with carbon–carbon double bonds are prepared from unsaturated diacids and diols. Subsequent appending of low molecular weight PEI by Michael addition gives target cationic polymers efficiently. Agarose gel retardation and fluorescence quenching assays show that these materials have good DNA binding ability and can completely retard plasmid DNA at weight ratio of 0.8. The formed polyplexes have appropriate sizes around 275 nm and zeta-potential values about +20–35 mV. The cytotoxicities of these polymers assayed by MTT are much lower than that of 25 kDa PEI. In vitro transfection toward 7402, HEK293 and U-2OS cells show that polymer P1 may give dramatically higher transfection efficiency (TE) than 25 kDa PEI, especially in U-2OS cells, suggesting that such polymer might be promising non-viral gene vectors.

Graphical abstractNovel low molecular weight PEI-appended biodegradable polymers were prepared and applied as non-viral gene vectors. Compared to 25 kDa PEI, these polymers have much higher transfection efficiency and lower cytotoxicity.Figure optionsDownload full-size imageDownload as PowerPoint slide