Aqueous-stable Mn(II)-MOF nanoparticles with high r₁ relaxivity and biocompatibility: a novel T₁ MRI contrast agent

The demand for safe, effective, and multifunctional magnetic resonance imaging (MRI) contrast agents (CAs) continues to drive the search for gadolinium-free alternatives. Here, we report the development of BVR-19-Mn, a novel, hydrolytically stable metal-organic framework (MOF) constructed from manganese (Mn(II)) and the amino acid L-cystine via a green, aqueous, room-temperature synthesis. BVR-19-Mn exhibits a high r₁ relaxivity of 4.98 mM^-1 s^-1 in water at 3 T and 25 °C, outperforming clinically approved gadolinium-based CAs such as Dotarem® under identical conditions. The enhanced relaxivity arises from a dense framework of Mn(II) centers, efficient water accessibility to internal pores, and favorable rotational dynamics inherent to its crystal structure. Importantly, BVR-19-Mn also demonstrates catalase-like activity, rapidly decomposing hydrogen peroxide into molecular oxygen, offering a mechanism to relieve tumor hypoxia. In vitro cytotoxicity and in vivo developmental zebrafish studies confirm biocompatibility across clinically relevant concentration ranges, with low toxicity observed at high dosing concentrations. Collectively, our findings position BVR-19-Mn as a high-performance MRI CA, introducing a sustainable, multifunctional platform for precision biomedical imaging.