Ultra-small-sized iron oxide nanoparticles with good biocompatibility are regarded as promising alternatives for the gadolinium-based contrast agents, which are widely used as a positive contrast agent in magnetic resonance imaging (MRI). However, the current preparation of the iron oxide magnetic nanoparticles with small sizes usually involves organic solvents, increasing the complexity of hydrophilic ligand replacement and reducing the synthesis efficiency. It remains a great challenge to explore new iron oxide nanoparticles with good biocompatibility and a high T1 contrast effect. Here, we reported a cage-like protein architecture self-assembled by approximately 6-7 BSA (bovine serum albumin) subunits. The BSA nanocage was then used as a biotemplate to synthesize uniformed and monodispersed Fe2O3@BSA nanoparticles with ultra-small sizes (∼3.5 nm). The Fe2O3@BSA nanoparticle showed a high r1 value of 6.8 mM-1 s-1 and a low r2/r1 ratio of 10.6 at a 3 T magnetic field. Compared to Gd-DTPA, the brighter signal and prolonged angiographic effect of Fe2O3@BSA nanoparticles could greatly benefit steady-state and high-resolution imaging. The further in vivo and in vitro assessments of stability, toxicity, and renal clearance indicated a substantial potential as a T1 contrast agent in preclinical MRI.
Keywords: BSA nanocage; T1 contrast agent; biocompatibility; magnetic resonance angiography; renal clearance; ultra-small iron oxide nanoparticles.