A Dual‐Locked Tandem Fluorescent Probe for Imaging of Pyroptosis in Cancer Chemo‐Immunotherapy

Abstract 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.