A triarylboron-based fluorescence probe for distinguishing inflammatory and tumor cells by imaging mitochondrial DNA and hypochlorite with different signal emission characteristics.

BACKGROUND

Mutations in the mitochondrial DNA (mtDNA) are linked to hereditary diseases and serve as danger associated molecular patterns involved in inflammation, autoimmunity, and aging. Mitochondrial HClO is particularly important in maintaining redox homeostasis. Furthermore, a growing body of evidence has established a strong link between HClO and various biological and pathological activities, ranging from inflammatory diseases to cancer, in addition to immune and neurological diseases. The simultaneous imaging of mitochondrial DNA (mtDNA) and hypochlorous acid (HClO) using different fluorescent signals can provide valuable information for the identification of inflammation or tumors.

RESULTS

In this study, two triaryboron (TAB)-based fluorescent probes, namely TAB-6-TP and TAB-4-TP, were synthesized to selectively image mitochondrial DNA and HClO. Both probes selectively respond to DNA by exhibiting significant fluorescence enhancement, but with varying degrees of blue shifts. Although their fluorescence responses to HClO are relatively small, the products of their reactions with HClO can bind to various negatively charged substances present in the cells, resulting in significant fluorescence enhancement and a corresponding blue shift. TAB-4-TP provided more differentiated signals than TAB-6-TP for both the DNA and HClO induced reactions. TAB-4-TP was therefore considered more suitable for cell imaging because it can distinguish inflammatory and tumor cells from normal cells with greater signal differences. Finally, co-localization experiments demonstrated strong fluorescence signals in tumor and inflammatory cells originating from the mitochondria.

SIGNIFICANCE: This study provides a strategy for distinguishing inflammatory cells from tumor cells, which can help in more accurate diagnosis of related diseases.