Fusion of magnetic fusogenic liposomes with model membranes for nanoparticle delivery

Efficient cytosolic delivery of magnetic nanoparticles (MNPs) remains a major challenge, as their endosomal sequestration severely limits magnetic heating and intracellular manipulation. Here, we report a new approach based on cationic fusogenic liposomes enabling the direct transfer of MNPs through lipid membrane fusion. MNP encapsulation within cationic liposomes yielded magnetic fusogenic liposomes (MFLs), whose interactions with model membranes (e.g., anionic or zwitterionic Large Unilamellar Liposomes, LUVs) were investigated using dynamic light scattering titration, isothermal titration calorimetry, and fluorescence resonance energy transfer (FRET) monitored by confocal microscopy. Magnetophoresis measurements quantified the magnetic load before and after fusion. The results demonstrate that the initial electrostatic attraction between oppositely charged membranes governs both lipid mixing and magnetic cargo transfer. This fusion-based delivery route provides an efficient and non-endosomal pathway for MNP transfers, offering new opportunities for magnetic hyperthermia, cellular engineering, and organelle-targeted manipulation.