Alkaline Phosphatase-Initiated Sensitive Responsiveness of Activatable Probes to Hydrogen Sulfide for Accurate Cancer Imaging and Differentiation
Alkaline Phosphatase-Initiated Sensitive Responsiveness of Activatable Probes to Hydrogen Sulfide for Accurate Cancer Imaging and Differentiation
复制标题
碱性磷酸酶引发的可激活探针对硫化氢的敏感响应，用于准确的癌症成像和分化
DOI：
10.31635/ccschem.022.202201971
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发表时间：
2022-06-30
期刊：
影响因子：
11.2
通讯作者：
Zhao, Chunchang
中科院分区：
文献类型：
--
作者：
Wang, Rongchen;Yin, Kai;Zhao, Chunchang
分子探针光学成像正在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表现出有限的敏感性、特异性和准确性，因为它们对基于生物标记物的成像的单一刺激具有典型的响应性。在这项研究中，我们开发了一种新的分子探针，显示碱性磷酸酶(ALP)指示对硫化氢的敏感响应，以用于准确的癌症成像和鉴别。这种设计的探头在生理条件下处于聚集态，表面带负电，对H_2S的光学响应较差。碱性磷酸酶介导的去磷酸化反应产生具有正电荷表面的组装产物，提供显著的聚集增强的对硫化氢的响应，并在755 nm处发光的近红外荧光。这种组装的探针电荷从负到正的反转对于基于ALP上调和硫化氢含量的差异对癌症的精确可视化和区分起着至关重要的作用。我们预计，我们的多参数激活分子探针电荷反转策略将有助于提高癌症成像的特异性和精确度。
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].