The Study on the Cellular Uptake Pathways of [Co(NTB)Cl]Cl-DNA Aggregates

Metal complexes may become a new type of promising gene delivery systems because of their low cytotoxicity, structural diversity, controllable aqua- and lipo-solubility, and appropriate density and distribution of positive charges. We previously constructed a series of Metal (?) complexes of polybenzimidazoles, especially the dinuclear Co2+ complexes of polybenzimidazole ligands which were suggested to be the most potential nonviral gene carrier based on our previous work. The cellular uptake pathway of a gene vector is an important factor in transgene expression. Here in, we investigated the cellular uptake pathways of [Co(NTB)Cl]Cl-DNA aggregates into COS-7 cells by using the specific inhibitors. These inhibitors were applied to selectively inhibit uptake pathways by Clathrin-mediated endocytosis (CME), Caveolae-mediated endocytosis (CvME), macropinocytosis and microtubules. Meanwhile, we also investigated the cellular uptake pathways of PEI-DNA and lipofectamine 2000-DNA (Lipofect-DNA) aggregates into COS-7 cells as positive controls. Investigation of transgene expression showed that the [Co(NTB)Cl]Cl-DNA aggregates into COS-7 cells were mainly dependent on caveolae-mediated endocytosis (CvME) and macropinocytosis.