Uptake Pathways of Guandinylated Disulfide Containing Polymers as Nonviral Gene Carrier Delivering DNA to Cells.

Polymers of guanidinylated disulfide containing poly(amido amine)s (Gua-SS-PAAs), have shown high transfection efficiency and low cytotoxicity. Previously, we synthesized two Gua-SS-PAA polymers, using guanidino containing monomers (i.e., arginine and agmatine, denoted as ARG and AGM, respectively) and N,N'-cystaminebisacrylamide (CBA). In this study, these two polymers, AGM-CBA and ARG-CBA were complexed with plasmid DNA, and their uptake pathway was investigated. Complexes distribution in MCF-7 cells, and changes on cell endosomes/lysosomes and membrane after the cells were exposed to complexes were tested. In addition, how the transfection efficiency changed with the cell cycle status as well as endocytosis inhibitors were studied. The polymers of AGM-CBA and ARG-CBA can avoid endosomal/lysosomal trap, therefore, greatly delivering plasmid DNA (pDNA) to the cell nucleoli. It is the guanidine groups in the polymers that enhanced complexes' permeation through cell membrane with slight membrane damage, and targeting to the nucleoli. J. Cell. Biochem. 118: 903-913, 2017. © 2016 Wiley Periodicals, Inc.