Ultra-small manganese dioxide nanoparticles with high T 1 relaxivity for magnetic resonance angiography.

Gadolinium (Gd)-based contrast agents (CAs) for clinical magnetic resonance imaging are facing the problems of low longitudinal relaxivity ( r 1 ) 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 r 1 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 (MnO 2 /PAA NPs), which exhibited good biocompatibility and high r 1 values. A series of MnO 2 /PAA NPs with different particle sizes were prepared and the relationship between the particle size and r 1 was studied, revealing that the MnO 2 /PAA NPs with a particle size of 4.9 nm exhibited higher r 1 . The finally obtained MnO 2 /PAA NPs had a high r 1 value (29.0 Mn mM -1 s -1 ) and a low r 2 / r 1 ratio (1.8) at 1.5 T, resulting in a strong T 1 contrast enhancement. In vivo magnetic resonance angiography with Sprague-Dawley (SD) rats further proved that the MnO 2 /PAA NPs showed better angiographic performance at low-dosage administration than commercial Gadovist® (Gd-DO3A-Butrol). Moreover, the MnO 2 /PAA NPs could be rapidly cleared out after imaging, which effectively minimized the toxic side effects. The MnO 2 /PAA NPs are promising candidates for MR imaging of vascular diseases.