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.

分子探针的光学成像正成为推进生物学研究和临床应用的重要工具。然而，目前大多数可用的分子探针由于其对基于生物标志物成像的单一刺激的典型响应性而显示出有限的灵敏度、特异性和准确性。在这项研究中，我们开发了一种新型分子探针，该探针显示碱性磷酸酶 (ALP) 指导的对硫化氢的敏感反应，可用于准确的癌症成像和分化。这种在生理条件下处于聚合状态的设计探针带有带负电荷的表面，对 H _{2的光学响应很差}S. ALP 介导的去磷酸化反应产生具有带正电荷的表面的组装产物，在 755 nm 处具有发光的 NIR 荧光，对 H ₂ S 具有显着的聚集增强响应性。_{这种组装探针从负到正的电荷反转在允许基于 ALP 上调和 H 2} S 含量差异的癌症的精确可视化和分化中起着至关重要的作用。我们设想我们的多参数激活分子探针的电荷反转策略将有助于提高癌症成像的特异性和精度。