Protease-specific nanosensors for magnetic resonance imaging.
Imaging of enzyme activity is a central goal of molecular imaging. With the introduction of fluorescent smart probes, optical imaging has become the modality of choice for experimental in vivo detection of enzyme activity. Here, we present a novel high-relaxivity nanosensor that is suitable for in vivo imaging of protease activity by magnetic resonance imaging. Upon specific protease cleavage, the nanoparticles rapidly switch from a stable low-relaxivity stealth state to become adhesive, aggregating high-relaxivity particles. To demonstrate the principle, we chose a cleavage motif of matrix metalloproteinase 9 (MMP-9), an enzyme important in inflammation, atherosclerosis, tumor progression, and many other diseases with alterations of the extracellular matrix. On the basis of clinically tested very small iron oxide particles (VSOP), the MMP-9-activatable protease-specific iron oxide particles (PSOP) have a hydrodynamic diameter of only 25 nm. PSOP are rapidly activated, resulting in aggregation and increased T2*-relaxivity.
Schellenberger
Eyk
E
Department of Radiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. eyk.schellenberger@charite.de
Rudloff
Franziska
F
Warmuth
Carsten
C
Taupitz
Matthias
M
Hamm
Bernd
B
Schnorr
Jörg
J
D000595:Amino Acid Sequence; D001665:Binding Sites; D015374:Biosensing Techniques / Q000379:methods*; D019343:Citric Acid / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D012680:Sensitivity and Specificity; D055672:Static Electricity; D013379:Substrate Specificity
D005290:Ferric Compounds; C000499:ferric oxide; D019343:Citric Acid; D020780:Matrix Metalloproteinase 9