Enzyme responsive LipoCEST agents: assessment of MMP-2 activity by measuring the intra-liposomal water 1H-NMR resonance shift
Mobile proton containing solutes can be detected by MRI via Chemical Exchange Saturation Transfer(CEST)method. The CEST sensitivity is dramatically enhanced by using, as exchanging protons, the water molecules confined inside liposomes, properly shifted by a paramagnetic Shift Reagent. The chemical shift of the intraliposomal water resonance(?IL) is affected by the overall shape of the supramolecular system. Herein, it is shown that ?IL of a spherical LipoCEST acts as a sensitive reporter of the distribution of Streptavidin proteins anchored at the Liposomes'surface by biotinylated phospholipids.These observations prompted the design of a MMP-2 responsive LipoCEST agent as the Streptavidin moieties can be released from the Liposomes' surfaces when a properly tailored enzyme-cleavable peptide is inserted on the phospholipids before the terminal biotin residues. ?IL reports on the overall changes in the supramolecular architecture associated to the cleavage carried out by MMP-2.
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