Contrast-enhanced magnetic resonance angiography is a powerful and effective method to accurately diagnose carotid artery stenosis. Small molecular gadolinium (Gd)-based agents have reliable signal enhancement, but their short circulating time may result in a loss of image resolution due to insufficient vascular filling or contrast agent emptying. Here, we report an MRA imaging approach to diagnose carotid artery stenosis using long-circulating bovine serum albumin (BSA)-Gd2O3 nanoparticles (NPs). The BSA-Gd2O3 NPs synthesized by a simple biomineralization approach exhibit admirable monodispersity, uniform size, favorable aqueous solubility, good biocompatibility, and high relaxivity (14.86 mM-1 s-1 in water, 6.41 mM-1 s-1 in plasma). In vivo MRA imaging shows that outstanding vascular enhancement of BSA-Gd2O3 NPs (0.05 mmol Gd/kg, half the dose in the clinic) can be maintained for at least 2 h, much longer than Gd-DTPA. Vessels as small as 0.3 mm can be clearly observed in MRA images with high resolution. In a rat carotid artery stenosis model, the BSA-Gd2O3 NPs-based MRA enables the precise diagnosis of the severity and location and the therapeutic effect following the surgery of carotid artery stenosis, which provides a method for the theranostics of vascular diseases.
Keywords: BSA-Gd2O3 NPs; MRA; biomineralization; carotid artery stenosis.