The successful delivery of nucleic acids into cells and their availability at the intracellular sites of action remain
a major challenge in gene therapy, because cells are resistant to the uptake of genetic materials and contain a variety of
mechanisms that degrade nucleic acids. To develop a nonviral carrier, we have recently designed a series of metal complexes
with polybenzimidazole (pbzim) that serve as DNA-condensing agents. In this study, we prepared a group of
Co(II)-pbzim complexes that bear variable numbers of both positive charges and benzimidazole (bzim) groups. First, the
formation of condensates at varied molar ratios of complex to DNA was examined by multiple biophysical measurements
at pH 7.4. The results showed that the size, morphology, and surface charge of the condensates formed via a Co(II) complex
dose-dependent process can be controlled by utilization of different complexes. Then, the imaging examination performed
with both confocal and fluorescence microscope indicated that the DNA condensates can be internalized into cells.
Luciferase activity assay showed that the DNA condensates formed at 1:1 of molar ratio are in favor of cell transfection
because of their appropriate size, profile, and positive surface charges. The addition of the helper lipid DOPE can enhance
both cellular uptake of the condensates and expression of the transferred genes. The MTT data indicated that cytotoxicity
of both Co(II) complexes and condensates is enhanced with increasing positive charges and bzim groups. All the results
revealed that the physical properties, cell transfection, and cytotoxicity of the condensates are regulated by the positive
charges and bzim groups on the metal complexes.