A pH-Activatable MnCO₃ Nanoparticle for Improved Magnetic Resonance Imaging of Tumor Malignancy and Metastasis

Engineered magnetic nanoparticles have been extensively explored for magnetic resonance imaging (MRI) diagnosis of a tumor to improve the visibility. However, most of these nanoparticles display "always-on" signals without tumor specificity, causing insufficient contrast and false positives. Here, we provide a new paradigm of MRI diagnosis using MnCO₃ nanorhombohedras (MnNRs) as an ultrasensitive T₁-weighted MRI contrast agent, which smartly enhances the MR signal in response to the tumor microenvironment. MnNRs would quickly decompose and release Mn²⁺ at mild acidity, one of the pathophysiological parameters associated with cancer malignancy, and then Mn²⁺ binds to surrounding proteins to achieve a remarkable amplification of T₁ relaxivity. In vivo MRI experiments demonstrate that MnNRs can selectively brighten subcutaneous tumors from the edge to the interior may be because of the upregulated vascular permeation at the tumor edge, where cancer cell proliferation and angiogenesis are more active. Specially, benefiting from the T₂ shortening effect in normal liver tissues, MnNRs can detect millimeter-sized liver metastases with an ultrahigh contrast of 294%. The results also indicate an effective hepatic excretion of MnNRs through the gallbladder. As such, this pH-activatable MRI strategy with facility, biocompatibility, and excellent efficiency may open new avenues for tumor malignancy and metastasis diagnosis and holds great promise for precision medicine.