Schellenberger Eyk, Rudloff Franziska, Warmuth Carsten, Taupitz Matthias, Hamm Bernd, Schnorr Jörg
Department of Radiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Bioconjug Chem. 2008 Dec;19(12):2440-5. doi: 10.1021/bc800330k.
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.
酶活性成像乃是分子成像的核心目标。随着荧光智能探针的引入，光学成像已成为体内实验性检测酶活性的首选方式。在此，我们展示了一种新型的高弛豫率纳米传感器，它适用于通过磁共振成像对蛋白酶活性进行体内成像。在特定蛋白酶切割后，纳米颗粒迅速从稳定的低弛豫率隐身状态转变为具有粘附性、聚集性的高弛豫率颗粒。为证明该原理，我们选择了基质金属蛋白酶9（MMP - 9）的切割基序，MMP - 9是一种在炎症、动脉粥样硬化、肿瘤进展以及许多其他伴有细胞外基质改变的疾病中起重要作用的酶。基于经过临床测试的超小型氧化铁颗粒（VSOP），可被MMP - 9激活的蛋白酶特异性氧化铁颗粒（PSOP）的流体动力学直径仅为25纳米。PSOP能迅速被激活，导致聚集并增加T2*弛豫率。
