Non‐Invasive Diagnosis of Early Colorectal Cancerization via Amplified Sensing of MicroRNA‐21 in NIR‐II Window

Abstract Accurate, sensitive, and in situ visualization of aberrant expression level of low‐abundant biomolecules is crucial for early colorectal cancer (CRC) detection ahead of tumor morphology change. However, the clinical used colonoscopy and biopsy methods are invasive and lack of sensitivity at early‐stage of cancerization. Here, an amplified sensing strategy is developed in the second near‐infrared long‐wavelength subregion (NIR‐II‐L, 1500–1900 nm) by integrating DNAzyme‐triggered signal amplification technology and lanthanide‐dye hybrid system. In the early‐stage of CRC, the overexpressed biomarker microRNA‐21 initiates the NIR‐II‐L luminescence ratiometric signal amplification of the CRCsensor. The high sensitivity with a limit of detection (LOD) of 1.26 p m allows non‐invasive visualization of orthotopic colorectal cancerization via rectal administration, which achieves early and accurate in situ diagnosis at 2 weeks ahead of the in vitro histological results. This innovative approach offers a promising tool for early diagnosis and long‐term monitoring of carcinogenesis progression, with potential applications in other cancer‐related biomarkers.