In Vivo Tumor Visualization through MRI Off-On Switching of NaGdF₄–CaCO₃ Nanoconjugates

The development of high-performance contrast agents in magnetic resonance imaging (MRI) has recently received considerable attention, as they hold great promise and potential as a powerful tool for cancer diagnosis. Despite substantial achievements, it remains challenging to develop nanostructure-based biocompatible platforms that can generate on-demand MRI signals with high signal-to-noise ratios and good tumor specificity. Here, the design and synthesis of a new class of nanoparticle-based contrast agents comprising self-assembled NaGdF₄ and CaCO₃ nanoconjugates is reported. In this design, the spatial confinement of the T₁ source (Gd³⁺ ions) leads to an “OFF” MRI signal due to insufficient interaction between the protons and the crystal lattices. However, when immersed in the mildly acidic tumor microenvironment, the embedded CaCO₃ nanoparticles generate CO₂ bubbles and subsequently disconnect the nanoconjugate, thus resulting in an “ON” MRI signal. The in vivo performance of these nanoconjugates shows more than 60-fold contrast enhancement in tumor visualization relative to the commercially used contrast agent Magnevist. This work presents a significant advance in the construction of smart MRI nanoprobes ideally suited for deep-tissue imaging and target-specific cancer diagnosis.