AbstractChemotherapy‐induced enteritis is one of the side effects associated with cancer therapy, which significantly affects the treatment effect, but there is no effective clinical detection method that can early diagnose its occurrence and progression. Here, a series of second near‐infrared window (NIR‐II) hybrid nanosensors are designed that consisted of lanthanide nanoparticles and β‐Mo2C‐derived polymetallic oxomolybdate nanoclusters (Ln@POM). Based on the high sensitivity of POM to reactive oxygen species (ROS) closely related to chemotherapy‐induced enteritis, the NIR‐II luminescence intensity and lifetime of Ln@POM (Ln: Yb3+, Nd3+, Ho3+, Tm3+, Er3+) show excellent responsiveness to H2O2 and HClO with the detection limit down to 0.15 and 0.14 µm, respectively. Utilizing Nd@POM as a ROS‐activated NIR‐II nanosensor, the chemotherapeutic enteritis is successfully detected within 7 h after induction of chemotherapy drugs, which is significantly earlier than the gold standard method (immunohistochemistry, 24 h). These results demonstrate that the designed hybrid nanosensors are promising optical tools for the early diagnosis of ROS‐related diseases.
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