Oligoamines grafted hyperbranched polyether as high efficient and serum-tolerant gene vectors

•A series of oligoamines-g-HBPs were synthesized as non-viral gene vectors, which exhibited low cytotoxicity and high transfection efficiency.•BSA adsorption assay showed that oligoamines-g-HBPs had good resistance against protein adsorption.•TEPA-g-HBP showed much improved serum-tolerance even when the serum concentration was increased to 30%.

To develop low toxic, high efficient, and excellent serum-tolerant polycation gene delivery systems, a series of oligoamines grafted hyperbranched polyether (oligoamines-g-HBP) were synthesized by conjugating different oligoamines, including triethylenetetramine (TETA) and tetraethylenepentamine (TEPA), onto COOH-functionalized hyperbranched poly(3-ethyl-3-oxetanemethanol). It was found that oligoamines-g-HBP exhibited good buffering capacity, strong DNA binding and high resistance against protein adsorption. In vitro cytotoxicity measurement indicated that oligoamines-g-HBP had much lower cytotoxicity as compared with 25 kDa PEI. The transfection efficiency of TEPA-g-HBP/DNA complexes at a certain N/P ratio was significantly higher than that of 25 kDa PEI/DNA complexes. Interestingly, it was found that TEPA-g-HBP had much improved serum-tolerant capability as compared with 25 kDa PEI even when serum concentration was increased to 30%. Confocal laser images further showed that the amount of YOYO-1 labeled DNA in nuclei got increased with increasing the number of secondary amino ethylene groups in oligoamines-g-HBP. The oligoamines-g-HBP presented great potential as gene delivery vectors for further clinical applications.

Graphical abstractA series of oligoamines-g-HBPs were synthesized as non-viral gene vectors, which exhibited higher transfection efficiency than that of 25 kDa PEI in serum-free and 10% FBS condition. Especially, oligoamines-g-HBP also showed much improved serum-tolerance even when the serum concentration was increased to 30%.Figure optionsDownload full-size imageDownload as PowerPoint slide