Ultra-small manganese dioxide nanoparticles with high T1 relaxivity for magnetic resonance angiography

Abstract

Gadolinium (Gd)-based contrast agents (CAs) for clinical magnetic resonance imaging are facing the problems of low longitudinal relaxivity (r₁) and toxicity caused by gadolinium deposition. Manganese-based small molecule complexes and manganese oxide nanoparticles (MONs) are considered as potential alternatives to Gd-based CAs due to their better biocompatibility, but their relatively low r₁ values and complicated synthesis routes slow down their clinical translation. Herein, we presented a facile one-step co-precipitation method to prepare MONs using poly(acrylic acid) (PAA) as a coating agent (MnO₂/PAA NPs), which exhibited good biocompatibility and high r₁ values. A series of MnO₂/PAA NPs with different particle sizes were prepared and the relationship between the particle size and r₁ was studied, revealing that the MnO₂/PAA NPs with a particle size of 4.9 nm exhibited higher r₁. The finally obtained MnO₂/PAA NPs had a high r₁ value (29.0 Mn mM⁻¹ s⁻¹) and a low r₂/r₁ ratio (1.8) at 1.5 T, resulting in a strong T₁ contrast enhancement. In vivo magnetic resonance angiography with Sprague-Dawley (SD) rats further proved that the MnO₂/PAA NPs showed better angiographic performance at low-dosage administration than commercial Gadovist® (Gd-DO3A-Butrol). Moreover, the MnO₂/PAA NPs could be rapidly cleared out after imaging, which effectively minimized the toxic side effects. The MnO₂/PAA NPs are promising candidates for MR imaging of vascular diseases.