A dual-locked tandem fluorescent probe for imaging of pyroptosis in cancer chemo-immunotherapy

• Main Authors: Wang, Xinzhu, He, Shasha, Cheng, Penghui, Pu, Kanyi
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science::Chemistry; Activatable Fluorescent Probes; Cancer Chemo-Immunotherapy
• Online Access: https://hdl.handle.net/10356/166273
• Institution: Nanyang Technological University

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.