Phase transformations in lipids confined to colloidally stable nanoscale particles

Lipids – biological, amphiphilic molecules with ability to self-organize into bilayer structures – have found lasting therapeutic application in drug-laden nanoparticles. Of recent interest is the internal structure of these nanoparticles, which influences their endosomal escape in cellular delivery pathways. Lipid nanoparticles with bicontinuous cubic internal structure show improved gene knockdown efficiency over more traditional liposomal particles [1]. Inverse hexagonal-phase lipid materials show further improved fusogenic properties, but are toxic due to pore formation with the plasma membrane [2]. Here we report a lipid-based material with phase-triggering character to avoid such toxicity limitations. In this system, a change from bicontinuous cubic to inverse hexagonal within the nanoparticles can potentially be triggered at any delivery step without requiring endosomal acidification. Instead, local heating is achieved via near-infrared radiation of incorporated gold nanorods, inciting localized surface plasmon resonance. The formulated lipid systems are characterized with cryogenic TEM and small-angle X-ray scattering (SAXS).

References:
[1] Kim, H. & Leal, C. (2015) ACS Nano. [2] Bouxsein, N. F. et al. (2007) Biochemistry.