Fig. 1.

Schematic representation of the cell entry of LNP–RNA complexes. (A) LNPs (red particle) enter the cells via endocytosis and are entrapped in the endosome (teal vesicle). Illustration credits: Alex D. Jerez, Imaging Technology Group at the Beckman Institute University of Illinois, Urbana-Champaign, IL. LNP–endosome membrane fusion involves a topological transformation of activation elastic energy $\mathrm{\Delta }{E}_{\mathit{fusion}}=-4\pi \overline{\kappa }$. (B) LNPs of different nanostructures (L, H_II, and Q_II) have distinct spontaneous curvature C₀, total curvature J, and Gaussian curvature K properties. (C) The escape of LNPs from endosomal entrapment will be enhanced by lowering the energetic barrier for fusion and fusion pore formation with the endosomal membrane for which Q_II LNPs should have preferential properties.