Figure 4.
A schematic representation of the cellular pathway and transfection mechanisms of different CL-NA complexes. The lamellar phases of CL-DNA complexes () enter the cells through endocytosis while the inverted hexagonal phases of CL-DNA complexes () rather directly interacts with the plasma membrane through facilitated fusion process. The fate of entered complexes (i.e. trapped in endosomes) turned out to be dependent on the membrane charge density (σM). High σM facilitates the fusion with the endosomal membrane effectively releasing DNA inside the cell, but increases the cytotoxicity at the same time. Low σM involves the low cytotoxicity but this state lacks the capability to escape out of the endosomes. On the other hand, the cubic phase of CL-siRNA complexes () show the high efficiency of escaping endosomes even at low σM, which arises from the negative Gaussian curvatures intrinsic to bicontinuous cubic structures.