Composition-tunable polycarboxylic acid-stabilized ultrasmall amorphous paramagnetic nanoclusters as multifunctional...

Conventional crystalline nanoscale magnetic resonance imaging (MRI) contrast agents (CAs) suffer from low longitudinal relaxivity (r ₁) and complex synthesis processes, limiting their clinical translation potential. Here, we report that polycarboxylic acid-stabilized ultrasmall amorphous paramagnetic nanoclusters (UAPNCs), fabricated via a one-step co-precipitation method, are proposed to simultaneously increase the number of inner-sphere coordinated water molecules (q), elevate the second-sphere hydrogen-bonded water molecules (q'), and prolong the rotational correlation time (τ _R), thereby achieving consistently excellent r ₁ (>20 mM^-1s^-1; 3.0 T) with a maximum of 41.27 ± 0.33 mM^-1s^-1 and low r ₂/r ₁ ratios (<3). Importantly, we propose a mechanism that non-paramagnetic metal doping further boosts r ₁ by approximately 40% via elevating q'. In vivo MRI reveals that manganese-based UAPNCs hold dual potential for hepatocyte-specific MRI and contrast-enhanced magnetic resonance angiography (CE-MRA), whereas gadolinium-based UAPNCs excel in CE-MRA. Overall, this work demonstrates the universality and superiority of UAPNCs as CAs, providing a new paradigm for designing next-generation MRI CAs.