Journal
ANALYTICAL CHEMISTRY
Volume 93, Issue 36, Pages 12434-12440Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.1c02591
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Funding
- National Natural Science Foundation of China [21974125, 21708035]
- National 111 Project of China [D20003]
- Collaborative Innovation Project of Zhengzhou (Zhengzhou University) [18XTZX12002]
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The probe constructed in this study utilizes mitochondrial microenvironments as inputs to generate fluorescence signals only when high pH and low polarity conditions are met simultaneously, providing a reliable method for cancer detection with reduced false positives. The probe also demonstrates increased affinity for cancer cell mitochondria due to the higher mitochondrial membrane potential in cancer cells, resulting in a high contrast fluorescence diagnosis ability of cancer at cellular and tissue levels exceeding clinic thresholds.
The ability to accurately diagnose cancer is the cornerstone of early cancer treatment. The mitochondria in cancer cells maintain a higher pH and lower polarity relative to that in normal cells. A probe that reports signals only when both conditions are met may provide a reliable method for cancer detection with reduced false positives. Here, we construct an AND logic gate fluorescent probe using mitochondrial microenvironments as inputs. Utilizing the hydrolysis of a coumarin scaffold, the probe generates fluorescence signals (ON) only when high pH (>7.0) and low polarity conditions exist simultaneously. Additionally, the higher mitochondrial membrane potential in cancer cells provides an additional level of selectivity because probe has increased affinity for cancer cell mitochondria. These capabilities endow the probe with a high contrast fluorescence diagnosis ability of cancer at cellular and tissue levels (as high as 51.9 fold), which is far exceeding the clinic threshold of 2.0 fold.
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