Enzyme-Responsive LipoCEST Agents: Assessment of MMP-2 Activity by Measuring the Intra-liposomal Water 1 H NMR Shift

Angew Chem Int Ed Engl. 2017 Sep 25;56(40):12170-12173. doi: 10.1002/anie.201706271. Epub 2017 Aug 25.

Abstract

Mobile proton-containing solutes can be detected by MRI by the chemical exchange saturation transfer (CEST) method. CEST sensitivity is dramatically enhanced by using, as exchanging protons, the water molecules confined inside liposomes, shifted by a paramagnetic shift reagent. The chemical shift of the intraliposomal water resonance (δIL ) is affected by the overall shape of the supramolecular system. δIL of a spherical LipoCEST acts as a sensitive reporter of the distribution of streptavidin proteins anchored at the liposome surface by biotinylated phospholipids. This finding prompted the design of a MMP-2 responsive LipoCEST agent as the streptavidin moieties can be released from the liposome surfaces when a properly tailored enzyme-cleavable peptide is inserted on the phospholipids before the terminal biotin residues. δIL reports on the overall changes in the supramolecular architecture associated to the cleavage carried out by MMP-2.

Keywords: LipoCEST; MMP-2; chemical shift; magnetic resonance imaging; paramagnetic liposomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biotin / chemistry
  • Liposomes / chemistry*
  • Matrix Metalloproteinase 2 / chemistry*
  • Phospholipids / chemistry
  • Proteolysis
  • Proton Magnetic Resonance Spectroscopy / methods*
  • Streptavidin / chemistry
  • Surface Properties
  • Water / chemistry

Substances

  • Liposomes
  • Phospholipids
  • Water
  • Biotin
  • Streptavidin
  • Matrix Metalloproteinase 2