Moving from nano‐ to micro‐systems may not just be a matter of scale, but it might imply changes in the properties of the systems that can open new routes for the development of efficient MRI contrast agents. This is the case reported in the present paper, where giant liposomes (giant unilamellar vesicles, GUVs) loaded with LnIII complexes have been studied as chemical exchange saturation transfer (CEST) MRI contrast agents. The comparison between nanosized liposomes (small unilamellar vesicles, SUVs) and GUVs sharing the same formulation led to differences that could not be accounted for only in terms of the increase in size (from 100–150 nm to 1–2 μm). Upon osmotic shrinkage, GUVs yielded a saturation‐transfer effect three order of magnitude higher than SUVs consistent with the increase in vesicles volume. Confocal microscopy showed that the shrinkage of GUVs resulted in multilamellar particles whereas SUVs are known to yield asymmetrical, discoidal shape.

A new class of liposomes (LipHosomes) is designed to induce a change of pH upon releasing their content. pH‐readout reports on the number of LipHosomes in the specimen. LipHosomes were prepared by entrapping NaOH or bicarbonate buffer in the intravesicular compartment. The liposomes suspension was purified from unentrapped compounds and brought to pH 7.0. The pH gradient between intra‐ and extra‐liposomal compartments is maintained because the phospholipidic membrane works as a semipermeable membrane thus preventing diffusion of ions across the membrane. The release of the liposomal content triggers a quantifiable variation of the pH of the medium. This feature has been harnessed in analytical assays based on ligand/anti‐ligand molecular recognition by exploiting the biotin‐streptavidin binding scheme. A pH difference of 0.2 units was observed upon the release of the payload from biotinylated LipHosomes bound to streptavidinated plates. The test showed an excellent sensitivity being able to reveal a concentration of bound LipHosomes in the sub‐pM range.

Moving from nano‐ to micro‐systems may not just be a matter of scale, but it might imply changes in the properties of the systems that can open new routes for the development of efficient MRI contrast agents. This is the case reported in the present paper, where giant liposomes (giant unilamellar vesicles, GUVs) loaded with LnIII complexes have been studied as chemical exchange saturation transfer (CEST) MRI contrast agents. The comparison between nanosized liposomes (small unilamellar vesicles, SUVs) and GUVs sharing the same formulation led to differences that could not be accounted for only in terms of the increase in size (from 100–150 nm to 1–2 μm). Upon osmotic shrinkage, GUVs yielded a saturation‐transfer effect three order of magnitude higher than SUVs consistent with the increase in vesicles volume. Confocal microscopy showed that the shrinkage of GUVs resulted in multilamellar particles whereas SUVs are known to yield asymmetrical, discoidal shape.

The Cover Feature shows a ligand/anti‐ligand assay where functionalized liposomes bind the analyte of interest. Next, a surfactant is added to damage the liposomal membrane and induce the release of the basic compound entrapped inside the vesicles so that a variation of the pH of bulk water occurs. The biotin–streptavidin binding scheme was used as a standard ligand/anti‐ligand model. This test is easy to carry out, low‐cost, and sensitive, with a detection threshold in the sub‐pM range. More information can be found in the Full Paper by Delli Castelli and co‐workers.