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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.
Wang et al. (Tue,) studied this question.