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.