title: Nanoparticle-based highly sensitive MRI contrast agents with enhanced relaxivity in reductive milieu.
abstract: Current magnetic resonance imaging (MRI) contrast agents often produce insufficient contrast for diagnosis of early disease stages, and do not sense their biochemical environments. Herein, we report a highly sensitive nanoparticle-based MRI probe with r1 relaxivity up to 51.7 ± 1.2 mM(-1) s(-1) (3T). Nanoparticles were co-assembled from Gd(3+) complexed to heparin-poly(dimethylsiloxane) copolymer, and a reduction-sensitive amphiphilic peptide serving to induce responsiveness to environmental changes. The release of the peptide components leads to a r1 relaxivity increase under reducing conditions and increases the MRI contrast. In addition, this MRI probe has several advantages, such as a low cellular uptake, no apparent cellular toxicity (tested up to 1 mM Gd(3+)), absence of an anticoagulation property, and a high shelf stability (no increase in free Gd(3+) over 7 months). Thus, this highly sensitive T1 MRI contrast nanoparticle system represents a promising probe for early diagnosis through possible accumulation and contrast enhancement within reductive extracellular tumour tissue.
authors.affiliation: Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056 Basel, Switzerland. cornelia.palivan@unibas.ch.
authors.forename: Severin J
authors.initials: SJ
authors.lastname: Sigg
authors.affiliation: Department of Radiology, Division of Radiological Physics, University of Basel Hospital, Petersgraben 4, 4031 Basel, Switzerland and Department of Biomedical Engineering, University of Basel, Basel, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Santini
authors.affiliation: Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056 Basel, Switzerland. cornelia.palivan@unibas.ch.
authors.forename: Adrian
authors.initials: A
authors.lastname: Najer
authors.affiliation: Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056 Basel, Switzerland. cornelia.palivan@unibas.ch.
authors.forename: Pascal U
authors.initials: PU
authors.lastname: Richard
authors.affiliation: Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056 Basel, Switzerland. cornelia.palivan@unibas.ch.
authors.forename: Wolfgang P
authors.initials: WP
authors.lastname: Meier
authors.affiliation: Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056 Basel, Switzerland. cornelia.palivan@unibas.ch.
authors.forename: Cornelia G
authors.initials: CG
authors.lastname: Palivan
mesh_terms: D003287:Contrast Media / Q000032:analysis / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053758:Nanoparticles / Q000032:analysis / Q000737:chemistry*
chemical_list: D003287:Contrast Media