Amphiphilic Azulene-Based Fluorescent Probe for Simultaneous Monitoring of Fluctuations in Carboxylesterase Activity in Diverse Biological Samples from a Single Organism

用于同时监测单一生物体不同生物样品中羧酸酯酶活性波动的两亲性薁基荧光探针

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Abstract

Carboxylesterase (CEs), as a key enzyme in ester metabolism, is simultaneously found with varying expression levels in diverse biological samples from a single organism, such as tissues, cells, bacteria and blood. However, the lack of integrated universal tools for the comprehensive detection of CEs'activity fluctuations in diverse biological samples from a single organism severely hinders the diagnosis and treatment of related diseases. Herein, we have developed an amphiphilic fluorescent probe (AZU-β) targeted toward CEs using an azulene derivative (AZU-OH) as a fluorophore. Using a "hydroxyl protection-deprotection" strategy, AZU-β incorporates a specific recognition group (acetyl ester) that activates the intramolecular charge transfer process to regulate the recognition signal toward CEs. AZU-β exhibits selectivity and highly sensitivity (the minimum detection limit is 1.8 × 10(-2) U/mL), as well as rapid response (within approximately 6.0 s), for detecting CEs'activity over a wide range from 1.8 × 10(-2) U/mL to 1.0 U/mL. Moreover, AZU-β exhibits outstanding water-oil amphiphilicity which makes it suitable for different biomembrane permeability levels. Therefore, AZU-β serves as an integrated universal tool that can not only detect CEs'activity at the serum level but also at cellular, tissue and bacterial levels under drug-induced liver injury conditions enabling the simultaneous monitoring of fluctuations in diverse biological samples from a single organism. It is expected that more probes targeting various disease-associated enzymes can be designed based on this amphiphilic design strategy to monitor relevant enzyme activity fluctuations in diverse biological samples from a single organism providing advanced analytical tools for related pathological research and diagnosis.

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