Figure 6.

Schematic illustration of the siRNA delivery pathway of CL–siRNA complexes. Cell attachment (I) is followed by endocytosis (II). Complexes in the endosome (III) need to escape into the cytoplasm to deliver their siRNA cargo. This is enabled by fusion of the membranes of the complex with the endosomal membrane, which results in pore formation (IV). The fusion process is aided by electrostatic attraction of endosomal and complex membranes (III) and the propensity of cubic phase-forming lipids to stabilize pore structures with negative Gaussian curvature. In the enlarged view of a pore and the schematic of the membrane structure of the gyroid cubic phase, blue and red lines indicate positive and negative curvature, respectively.