LAUSR

Real‐time imaging of programmed cancer cell death (PCD) is imperative to monitor cancer therapeutic efficacy and tailor therapeutic regimens; however, specific in vivo detection of intratumoral pyroptosis remains challenging. Herein, a dual‐locked and tandem activatable probe (DTAP) is reported for near‐infrared fluorescence (NIRF) imaging of intratumoral pyroptosis during cancer chemo‐immunotherapy in living mice. The probe comprises a hemicyanine dye dual‐locked with an enzyme‐responsive moiety that can be tandemly cleaved by pyroptosis‐related biomarker (Caspase‐1) and cancer biomarker (GGT) to turn on its NIRF signal. As pyroptosis plays a vital role in triggering anti‐tumor immune responses, the activated signal of DTAP correlates well with the population of tumor‐infiltrating cytotoxic T lymphocytes and tumor growth inhibition, consequently permitting the prediction of cancer therapeutic efficacy. This study also provides a non‐invasive technique to study the regulatory mechanism of pyroptosis in cancer therapy and to optimize cancer chemo‐immunotherapies for precision medicine.