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

ABSTRACT 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 Cr ³⁺ 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.