Nanogyroids Incorporating Multivalent Lipids: Enhanced Membrane Charge Density and Pore Forming Ability for Gene Silencing

The self-assembly of a custom-synthesized pentavalent cationic lipid (MVL5) and glycerol monooleate (GMO) with small interfering RNA (siRNA) results in the formation of a double-gyroid bicontinuous inverted cubic phase with colocalized lipid/siRNA domains as shown by synchrotron X-ray scattering and fluorescence microscopy. The high charge density (due to MVL5) and positive Gaussian modulus of the GMO-containing membranes confer optimal electrostatic and elastic properties for endosomal escape, enabling efficient siRNA delivery and effective, specific gene silencing.