Renal clearable ZDS@MnFe₂O₄ nanoprobes for cardiovascular disease imaging

Cardiovascular diseases with severe vascular stenosis or occlusion can lead to tissue hypoxia, multi-organ dysfunction, and high mortality, emphasizing the need for accurate and safe vascular imaging. While digital subtraction angiography and computed tomography angiography are widely used, they involve ionizing radiation and iodinated contrast agents, posing risks of nephrotoxicity and allergic reactions. Contrast-enhanced magnetic resonance angiography (CE-MRA) offers a non-ionizing alternative, but gadolinium-based agents are limited by rapid clearance, risks of nephrogenic systemic fibrosis, and CNS accumulation. Metal-doped superparamagnetic iron oxide nanoparticles (SPIONs) represent promising T₁ probes; however, conventional surface coatings often increase hydrodynamic size, limiting renal clearance. Here, we develop ultrasmall MnFe₂O₄ nanoparticles functionalized with zwitterionic dopamine sulfonate (ZDS), exhibiting excellent water solubility, high longitudinal relaxivity (R₁ = 5.47 mM⁻¹·s⁻¹), and a compact hydrodynamic diameter (~ 6 nm) suitable for renal elimination. Under clinical 3.0 T MRI, ZDS@MnFe₂O₄ enables high-resolution imaging of cervical and abdominal vasculature, resolving vessels as small as 0.38 mm up to 1-h post-injection. The outstanding imaging capability allows real-time monitoring of carotid recanalization and detection of acute superior mesenteric veins and deep vein thromboses. This platform offers a promising approach for advanced vascular diagnostics by striking an optimal balance among imaging performance, biosafety, and clinical practicality.