Lipid cubic mesophases combined with Superparamagnetic Iron Oxide Nanoparticles: a hybrid multifunctional platform with tunable magnetic properties for nanomedical applications

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Abstract
Hybrid materials composed of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) and lipid self-assemblies possess a considerable applicative potential in the biomedical field, specifically, for drug/nutrients delivery. In recent works we have shown that SPION-doped lipid cubic liquid crystals undergo a cubic-to-hexagonal phase transition under the action of temperature or of an alternating magnetic fields (AMF). This transition triggers the release of drugs embedded in the lipid scaffold or in the water channels. In this contribution, we address this phenomenon in depth, to fully elucidate the structural details and optimize the design of hybrid multifunctional carriers for drug delivery. Combining Small-Angle X-Ray Scattering (SAXS) with a magnetic characteri-zation, we find that in bulk lipid cubic phases the cubic-to-hexagonal transition determines the magnetic response of SPIONs. We then extend the investigation from bulk liquid-crystalline phases to colloidal dispersions, i.e. to lipid/SPIONs nanoparticles with cubic internal structure (“magnetocubosomes”). Through Synchrotron SAXS, we monitored the structural response of magnetocubosomes while exposed to an AMF: the magnetic energy, converted into heat by SPIONs, activates the cubic-to-hexagonal transition, and can thus be used as a remote stimulus to spike drug release “on-demand”. In addition, we show that the AMF-induced phase transition in magnetocubosomes steers the re-alignment of SPIONs into linear string assemblies and connect this effect with the change in their magnetic properties, observed at the bulk level. Finally, we assess the internalization ability and cytotoxicity of magnetocubosomes in vitro on HT29 ade-nocarcinoma cancer cells, in order to test the applicability of these smart carriers in drug delivery applications