OEI800 polyconjugates linked with ketalized glycolic acid for use as gene vectors

Abstract

Endosomal escape of DNA polyplexes is one prominent bottleneck involved in the transfection process. Purposely against the low pH level in the endosome compartment, a series of acid-cleavable gene vectors constructed from oligoethyleneimine OEI800 polyconjugates linked with ketalized glycolic acid were designed herein and termed OEI-GKs. Their potential as gene vectors was comparatively evaluated by investigating the properties including DNA binding ability, polyplexes zeta potential, particle size, acid-triggered degradation, buffer capability before and after degradation, cytotoxicity, and transfection efficiency. The resultant data indicate that the transfection efficiency and cell-biocompatibility are dependent on the polymer architecture and molecular weights, which can be tailored by adjusting the charge ratio of OEI800versus the linking agent. OEI-GK(1 : 1) can be potentially developed as efficient vectors for the gene delivery in terms of their transfection activity even higher than PEI25k as well as the negligible cytotoxicity. Those improved properties are believed to have association with ketal-associated degradation of OEI-GK under acid conditions in the endosome, which lead to not only easy unpacking of DNA from the hydrolyzed polyplexes but also, interestingly, substantially enhanced buffer capability.