LANTHANIDE-LOADED PARAMAGNETIC LIPOSOMES AS SWITCHABLE MAGNETICALLY ORIENTED NANOVESICLES

Magnetically oriented liposomes can be prepared by exposing unilamellar spherical systems loaded with paramagnetic lanthanide(ill) complexes to hyperosmotic stress. The resulting nonspherical, lens-shaped, nanoparticles can orient within a static magnetic field, depending on the magnetic properties of their membrane bilayer. The orientation of the vesicles can be easily determined by measuring the paramagnetic contribution to the H-1 chemical shift of the intraliposomal water proton resonance. As the latter shift is dominated by the bulk magnetic susceptibility contribution, its sign (negative or positive) reports about the preferred orientation adopted by the nanovesicles. The alignment within the field depends upon the magnetic susceptibility anisotropy of the liposome membrane, Delta(LIPO)(chi). When Delta(LIPO)(chi) has a negative value (e.g., for nonspherical liposomes made of conventional phospholipids), the nanoparticles align with their long axis parallel to the field, whereas when Delta(LIPO)(chi) > 0 the vesicles flip by 90 degrees. The sign of the chemical shift of the intraliposomal water resonance is positive in the former case and negative in the tatter, respectively. The liposome orientation can be switched by incorporating in the liposome bilayer suitable amphiphilic paramagnetic lanthanide(III) complexes. The sign of Delta(LIPO)(chi), and consequently the magnetic alignment, will correspond to the sign of the magnetic susceptibility anisotropy of the metal complex. The magnetic susceptibility anisotropy is dependent on both the electronic configuration of the lanthanide ion and the structural characteristics of the amphiphilic complex incorporated in the liposome membrane. The magnetic orientation of such vesicles is maintained in vivo, thus opening promising perspectives for the application of nonspherical liposomes in medical imaging.