title: Supramolecular protamine/Gd-loaded liposomes adducts as relaxometric protease responsive probes.
abstract: A new approach to enzyme-responsive MRI agents based on the use of liposomes loaded with a high number of paramagnetic metal complexes (Gd-HPDO3A) is presented. It relies on the disruption of low relaxivity aggregates formed by liposomes and a macromolecular substrate that is selectively cleaved by the enzyme of interest. The interaction of anionic liposomes composed of POPC:CHOL:DPGS and the cationic protein protamine yields a poorly soluble supramolecular assembly endowed with a low relaxivity. The action of the serine protease trypsin causes the digestion of protamine and the consequent de-assembly of the supramolecular adduct. The process is accompanied by an overall relaxation enhancement of solvent water protons as consequence of the dissolution of the aggregated liposomes. The observed increase of relaxivity is linearly dependent on the enzyme concentration. An illustrative example of the possible use of the herein presented responsive agent has been reported. It consists of the entrapment of the supramolecular assembly in alginate microcapsules that have often been used as envelopes for in vivo applications of stem cells and pancreatic islets. The change in the observed longitudinal relaxation rate R(1) (leading to an hyperintense signal in the corresponding MR images) may act as a sensor of the protease activity in the biological environment in which the capsules is located.
authors: Department of Life Sciences, Faculty of Sciences and Technology, and Center for Neurosciences and Cell Biology, University of Coimbra, PO Box 3046, 3001-401 Coimbra, Portugal.
authors: Sara
authors: S
authors: Figueiredo
authors: João Nuno
authors: JN
authors: Moreira
authors: Carlos F G C
authors: CF
authors: Geraldes
authors: Silvio
authors: S
authors: Aime
authors: Enzo
authors: E
authors: Terreno
mesh_terms: D003287:Contrast Media / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry; D006494:Heparin Antagonists / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods; D015335:Molecular Probes / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000378:metabolism; D010539:Permeability; D011479:Protamines / Q000737:chemistry; D011522:Protons; D014357:Trypsin / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D003287:Contrast Media; D006494:Heparin Antagonists; D006571:Heterocyclic Compounds; D008081:Liposomes; D015335:Molecular Probes; D009942:Organometallic Compounds; D011479:Protamines; D011522:Protons; C062402:gadoteridol; D014867:Water; D005682:Gadolinium; D010447:Peptide Hydrolases; D014357:Trypsin