Enzyme-Activated MRI for In Vivo Glucose Imaging via a Biodegradable Chromium Nanoprobe

Non-invasive visualization of glucose metabolism in living organisms remains a major challenge, as existing techniques cannot specifically detect glucose molecules with deep-tissue penetration and without ionizing radiation. To overcome this, we developed an enzyme-activated magnetic resonance imaging strategy (eaMRI) using a biodegradable nanoprobe, CrGOx@Lip, that integrates endogenous Cr³⁺ ions with glucose oxidase for glucose-responsive imaging. Our approach leverages GOx not only as a catalytic engine to specifically oxidize glucose but also as a structural template to guide the in-situ synthesis of a potent MRI reporter (paramagnetic chromium gluconate). This design enables direct, specific amplification of MRI signals in proportion to local glucose concentration, achieving an 8.28-fold relaxivity increase. We validated this method for sensitive glucose mapping in vivo, including delineating Warburg-effect-driven tumors and quantifying pathological glucose accumulation in metabolic dysfunction-associated fatty liver disease (ΔSNR% = 18.51 ± 3.72 vs. 1.14 ± 1.39 in controls; p <0.001), and further demonstrated its utility in monitoring therapeutic efficacy via glucose-responsive signal changes. By synergizing enzymatic precision with nanomaterial engineering, our CrGOx@Lip-mediated eaMRI platform provides a glucose-specific, radiation-free, and non-invasive strategy for sensitive metabolic diagnostics in precision medicine.