**1. Introduction**

Nanomedicine has provided many tools to reduce invasiveness and many acute and chronic side effects associated with chemotherapy while improving patients' quality of life [1]. The development of new nanosystems has clearly contributed to these advancements. A recent strategy is the combination of liposomes and hydrogels, that might provide better drug formulation stability and drug administration routes [2]. A more robust soft material is attained with the incorporation of magnetic nanoparticles. Such can be obtained, for example, through the combination with magnetoliposomes [3,4]. A different concept is the separate embedding of both nanoparticles and liposomes in the hydrogel matrix [3]. These strategies offer a means of developing multifunctional smart materials that can host membrane-bound enzymes/glycolipids, besides the targeting with a magnetic field gradient and the stimuli-responsiveness through the application of an alternating magnetic field [5]. The on-demand release from stimuli-responsive liposomes enables the use of more

potent drugs [6], while the hydrogel immobilizes the components and provides the local environment required to support cell growth [7]. Further, all the components can be independently adjusted, which allows, for example, for the evaluation of which hydrogel is better fitted for a certain composite and application [2]. However, the majority of the developed magnetic liposome-hydrogel complexes have been restricted to the use of polymeric matrices, mainly alginate, and no attention has been given to supramolecular hydrogels.

The self-assembly of supramolecular hydrogelators is driven towards a kinetically trapped intertwined fibrillar structure encompassing solvent pocket microdomains through the cooperative effect of different non-covalent intermolecular interactions [8,9]. The variety of non-covalent intermolecular interactions, both of liposomes and supramolecular hydrogels, might lead to complex behavior and less straightforward magnetic liposome-hydrogel formulation. Hereby, in this work three different hydrogelators (Figure 1A) known to be adequate for drug delivery [10,11] were evaluated as carrying matrixes of magnetoliposomes. Two different types of magnetoliposomes were developed, solid and aqueous, which are schematically represented in Figure 1B. The strategy employed to evaluate this proof-of-concept consisted in preparing the magnetoliposomes, confirming their formation and posterior gelation of the supramolecular hydrogel under the presence of a dilute solution of magnetoliposomes, thus ensuring that the dominant observed effects are exerted by the hydrogel network (or hydrogelator) over the magnetoliposomes membrane (Figure 1C).

**Figure 1.** (**A**) Hydrogelator molecules used in this work. Legend: Npx: naproxen; Phe: phenylalanine; Ala: alanine; G: glycine; R: arginine; D: aspartate; ΔAbu: dehydroaminobutyric acid; ΔPhe: Dehydrophenylalanine. (**B**) Schematic representation of the aqueous and solid magnetoliposomes. (**C**) Schematic representation of the strategy used for the development of the supramolecular magnetic liposome-hydrogel complexes.
