An NIR-Fluorophore-Based Theranostic for Selective Initiation of Tumor Pyroptosis-Induced Immunotherapy

Abstract Pyroptosis is an inflammatory form of programmed cell death that can effectively eliminate malignant cells and boost anticancer immunity. However, most of the current pyroptosis inducers lack cell selectivity, which may cause severe side effects for cancer therapy. In this work, for the first time, we discovered that the commonly used near-infrared (NIR) fluorogenic hemicyanine (CyNH2) induces pyrolysis to kill cancer cells and boost antitumor immunity. Cancer cells overexpressing the NAD(P)H: quinone oxidoreductase isozyme 1 (NQO1)-responsive theranostic (NCyNH2) were designed for selective cell pyroptosis and were nonfluorescent with low toxicity before activation. In the presence of NQO1, the fluorescence of CyNH2 was restored and could selectively initiate pyroptosis of cancer cells and further lead to systemic antitumor immunity activation for solid tumor therapy. Thus, this fluorogenic NIR dye may represent a novel theranostic agent for the selective initiation of tumor pyroptosis.