The inclusion of superparamagnetic iron oxide nanoparticles (SPIONs) in lipid mesophases is a promising strategy for drug-delivery applications, combining the innate biocompatibility of lipid architectures with SPIONs' response to external magnetic fields. Moreover, the organization of SPIONs within the lipid scaffold can lead to locally enhanced SPIONs concentration and improved magnetic response, which is key to overcome the current limitations of hyperthermic treatments. Here we present a Small-Angle X-ray Scattering (SAXS) structural investigation of the thermotropic and magnetotropic behavior of glyceryl monooleate (GMO)/water mesophases, loaded with hydrophobic SPIONs. We prove that even very low amounts of SPIONs deeply alter the phase behavior and thermotropic properties of the mesophases, promoting a cubic to hexagonal phase transition, which is similarly induced upon application of an Alternating Magnetic Field (AMF). Moreover, in the hexagonal phase SPIONs spontaneously self-assemble within the lipid scaffold into a linear supraparticle. This phase behavior is interpreted in the framework of the Helfrich's theory, which shows that SPIONs affect the mesophase both from a viscoelastic and from a structural standpoint. Finally, the dispersion of these cubic phases into stable magnetic colloidal particles, which retain their liquid crystalline internal structure, is addressed as a promising route towards magneto-responsive drug-delivery systems (DDS).

This contribution reviews the state of art on hybrid soft matter assemblies composed of inorganic nanoparticles (NP) and lamellar or non-lamellar lipid bilayers.

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Hybrid materials composed of superparamagnetic iron oxide nanoparticles (SPIONs) and lipid self-assemblies possess considerable applicative potential in the biomedical field, specifically, for drug/nutrient delivery. Recently, we showed that SPIONs-doped lipid cubic liquid crystals undergo a cubic-to-hexagonal phase transition under the action of temperature or of an alternating magnetic field (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 characterization, 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 monitor 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 realignment 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 adenocarcinoma cancer cells, in order to test the applicability of these smart carriers in drug delivery applications.