Controlled intracellular self-assembly of gadolinium nanoparticles as smart molecular MR contrast agents.

Herein we developed a new “smart” Gd-based MR contrast agent (i.e., 1) which is susceptive to furin, a protease overexpressed in tumor. Under the action of furin, 1 condenses to form dimers (1-Ds) and the latter self-assemble into gadolinium nanparticles (Gd-NPs). Relaxivity of 1-D is more than 2 folds of those of 1 and magnevist at 1.5 T, and 1.4 folds of that of 1 at 3 T. Intracellular condensation of 1 in furin-overexpressed MDA-MB-468 cells was proven with direct two-photon laser microscopy (TPLM) fluorescence imaging of the cells incubated with the europium analog of 1 (i.e., 2). Intracellular Gd-NPs of 1 were uncovered and characterized for the first time. MRI of MDA-MB-468 tumors showed that 1 has enhanced MR contrast within the tumors than that of its scrambled control 1-Scr.

在此，我们开发了一种新的“智能”基于钆的磁共振造影剂（即1），它对弗林蛋白酶敏感，弗林蛋白酶是一种在肿瘤中过度表达的蛋白酶。在弗林蛋白酶的作用下，1发生缩合形成二聚体（1 - Ds），后者自组装成钆纳米颗粒（Gd - NPs）。1 - D在1.5T时的弛豫率是1和马根维显的2倍多，在3T时是1的1.4倍。通过对用1的铕类似物（即2）孵育的细胞进行直接双光子激光显微镜（TPLM）荧光成像，证明了1在弗林蛋白酶过度表达的MDA - MB - 468细胞内发生缩合。首次发现并表征了1在细胞内形成的Gd - NPs。对MDA - MB - 468肿瘤的磁共振成像显示，1在肿瘤内比其乱序对照物1 - Scr具有更强的磁共振造影效果。