Alkaline Phosphatase-Initiated Sensitive Responsiveness of Activatable Probes to Hydrogen Sulfide for Accurate Cancer Imaging and Differentiation

Optical imaging with molecular probes is becoming an essential tool for advancing biological research and clinical applications. However, most currently available molecular probes show limited sensitivity, specificity, and accuracy due to their typical responsiveness to a single stimulation for biomarker-based imaging. In this study, we develop a novel molecular probe that shows alkaline phosphatase (ALP)instructed sensitive responsiveness to hydrogen sulfide for accurate cancer imaging and differentiation. This designed probe in an aggregated state under physiological conditions bears negatively charged surfaces, giving poor optical response to H2S. The ALP-mediated dephosphorylation reaction yields an assembled product with a positively charged surface, affording significantly aggregation-enhanced responsiveness to H2S with light-up NIR fluorescence at 755 nm. Such charge reversal of assembled probe from negative to positive plays a vital role in allowing precise visualization and differentiation of cancers based on differences in ALP upregulation and H2S content. We envisage that our charge-reversal strategy for multiple-parameter-activated molecule probes will facilitate boosting the specificity and precision of cancer imaging. [GRAPHICS] .

Automated summary

In this study, a novel molecular probe with alkaline phosphatase (ALP) instructed sensitive responsiveness to hydrogen sulfide (H2S) was developed for accurate cancer imaging and differentiation. The probe showed a charge reversal from negative to positive through ALP-mediated dephosphorylation reaction, resulting in enhanced responsiveness and visualization of H2S.