An SMVT-targeting and peroxynitrite-activating fluorescent probe for head and neck cancer imaging and peroxynitrite detection

Abstract Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide. For better diagnosis and precise resection of HNSCC, Fluorescent probe has been developed as an ideal tool to visualize tumor sites and to detect biological molecules. However, the targeting strategies of small molecular probes are limited. We designed probe RB-PN (Rhodamine biotin-peroxynitrite) with both sodium-dependent multivitamin transporter (SMVT)-targetable and peroxynitrite (ONOO−)-activatable tumor-targeting strategies. It can detect ONOO− with high specificity and selectivity, and rapid response. Besides, it exhibits prominent imaging abilities with enhanced accumulation by SMVT-transportation. The remarkable sensitivity, selectivity, turn-on signal change and rapid responsive time have been identified. We evidenced the dual-targeting strategy, and applied it in tumor visualization and ONOO− detection both in HNSCC cells and in vivo. We also identified the potential application of it in cytokine therapy using 3D micro-spheroid models. We expect RB-PN with a dual-targeting strategy could be conducive to the diagnosis of tumor pre-operatively or even intra-operatively.