Magnetic resonance angiography based on iron-coordinated poly(amino acid)s nanoprobes: an in vitro and in vivo experimental study

Objectives To develop a gadolinium-free T1-weighted magnetic resonance (MR) contrast nanoprobe using Fe(III)-poly(amino acid)s-coordinated complexes (Fe@polyDOPA- b -polysarcosine, Fe@POS) for high-resolution MR angiography (MRA) with an extended imaging window. Materials and methods Fe@POS nanoprobes were prepared by the self-assembly of Fe(III) and polyDOPA- b -polysarcosine copolymers. Physicochemical and cytological characterizations were conducted to demonstrate their feasibility for MRA. MRA of the aorta was conducted on New Zealand rabbits, which were divided into one experimental group ( n = 3) receiving Fe@POS nanoprobes and one control group ( n = 3) receiving Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). Cardiac and hepatic MR acquisition were conducted on Bama Swine ( n = 3). Long-term biodistribution ( n = 3) and biosafety ( n = 4) evaluation was performed on BALB/c mice. Short-term and acute toxicity evaluation was conducted on BALB/c mice ( n = 5) and Bama pigs ( n = 3). Results Fe@POS nanoprobes exhibited a regular nanomicelle structure with an average particle size of 25 nm. Compared with Gd-DTPA (r 1 = 4.38 mM -1 s -1 ), Fe@POS nanoprobes exhibited higher longitudinal relaxivity (r 1 = 5.74 mM -1 s -1 ). In rabbit models, significant MR signal enhancement was observed in the abdominal aorta for over 4 h post-injection of Fe@POS. In porcine models, prolonged T1 enhancement was observed on MRA of the cardiovascular system, revealing detailed arterial and venous vasculature system in MR images. The biosafety evaluations demonstrated that the Fe@POS nanoprobes exhibited satisfactory biocompatibility and no prolonged iron accumulation in major organs under the tested conditions. Conclusion Fe@POS nanoprobes simultaneously provided high-resolution T1-weighted MRA of the cardiovascular system with an extended imaging window. Key Points Question Can a gadolinium-free nanoprobe provide prolonged high-resolution T1-weighted magnetic resonance angiography? Findings The use of Fe (III)-based poly(amino acid)s nanoprobes enables high-spatial-resolution magnetic resonance angiography of the cardiovascular system with a long window period. Critical Relevance The development of this new MRI contrast agent could broaden its clinical applicability and contribute to more precise diagnoses of cardiovascular diseases.