The conjugation of copper and zinc ions with the PAMAM-Pyrr dendrimer increased its potential from practically neutral to 4.0 ± 1.6 mV for (CuSO4)18@DAB-dendr-(Pyrr)64 and 4.6 ± 0.3 mV for (ZnCl2)22@DAB-dendr-(Pyrr)64, respectively. The addition of (CuSO4)18@DAB-dendr-(Pyrr)64 dendrimer to control siRNA in a range of (0.5-170):1 molar ratio led to a significant increase in zeta potential from -18.1 ± 8.4 to 2.4 ± 0.4 mV. The zeta potential reached a plateau at siRNA:dendrimer molar ratios of 1:(70-80) (Figure3, upper panel). The addition of (ZnCl2)22@DAB-dendr-(Pyrr)64 dendrimer to control siRNA in a range of (0.5-300):1 molar ratio also led to a significant increase in zeta potential from -16.1 ± 3.3 to -1.5 ± 0.3 mV. Interestingly, the zeta potential of the siRNA:(ZnCl2)22@DABdendr-(Pyrr)64 complex never became positive. It seems that siRNA is able to cover all positive charges on the surface of dendrimers. With the addition of further aliquots of the (ZnCl2)22@DAB-dendr-(Pyrr)64 dendrimer, an increasing peak characteristic for free siRNA and a second, decreasing for the complex was observed. This may indicate weak interactions between the tested dendrimer and the added genetic material. As the addition of subsequent portions of the dendrimer did not lead to the formation of a more stable complex, the titration was discontinued and it was assumed for further studies that the siRNA:(ZnCl2)22@DABdendr-(Pyrr)64 dendrimer complex reaches a plateau at molar ratios of 1:(200-220) (Figure3, lower panel). The fact that the dendriplex did not achieve a positive charge upon titration by (ZnCl2)22@DAB-dendr-(Pyrr)64 dendrimer means that the dendriplexes formed by (ZnCl2)22@DAB-dendr-(Pyrr)64 dendrimer may have a lower tendency to interact with the cell membrane and therefore, also have a lower transfection efficiency.