Beta-galactosidase-responsive synthetic biomarker for targeted tumor detection

Nishihara, Tatsuya; Kuno, Satoshi; Nonaka, Hiroshi; Tabata, Satoshi; Saito, Natsumi; Fukuda, Shinji; Tomita, Masaru; Sando, Shinsuke; Soga, Tomoyoshi

doi:10.1039/c8cc06068a

Cited by 9 publications

(5 citation statements)

References 27 publications

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“…Among these specific enzymes, β-galactosidase (β-gal) is widely known as a common kind of hydrolase in cells and the main biological function of β-gal is to remove galactose residues from substrates ( Komatsu and Urano, 2015 ). In recent years, β-gal has attracted extensive attention as a vital enzyme biomarker because it has been shown to be overexpressed in senescent cells, tumor cells as well as in Escherichia coli ( E.coli ) ( Munoz-Espin and Serrano, 2014 ; Chen et al, 2016 ; Gu et al, 2016 ; Adkins et al, 2017 ; Nishihara et al, 2018 ). Therefore, developing efficient methods to detect β-gal with high efficiency and specificity is thus of great importance for the early diagnosis of the specific diseases and the identification of E.coli infection.…”

Section: Introductionmentioning

confidence: 99%

An enzyme-activatable dual-readout probe for sensitive β-galactosidase sensing and Escherichia coli analysis

Huang

Feng

Zhang

et al. 2022

Front. Bioeng. Biotechnol.

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Rapid and accurate sensing of β-galactosidase (β-gal) activity is particularly critical for the early detection of many diseases and has become a topic of interest in recent years. However, most traditional probes for β-gal sensing often suffer from the disadvantages of narrow dynamic range, low reaction efficiency and are only employed with either colorimetric or fluorescence sensing. Furthermore, β-galactosidase sensing based assay for efficient detection and antibiotic resistance analysis of Escherichia coli (E.coli) is not available. Here, an enzyme-induced probe assay was reported for dual sensitive fluorescence and colorimetric measurement of β-gal activity, and was further employed for detection of Escherichia coli and their antibiotic resistance analysis. The DCM-βgal probe was virtually non-emissive in aqueous solution, while it could be activated by β-gal to produce bright emission. Under optimized conditions, DCM-βgal displayed high sensitivity, selectivity and rapid response to β-gal with a low detection limit of 1.5 × 10−3 U ml−1. Importantly, this assay was successfully applied to sensitive detection of E. coli cells with a fast detection process within 5 h and a low detection concentration of 1 × 103 CFU ml−1. Furthermore, the enzyme-activatable assay was also successfully applied for high throughput E. coli antibiotic resistance analysis. The DCM-βgal strategy is applied for the first time on the detection of E. coli cells and their antibiotic resistance analysis. It is provided with the advantages of high selectively, a simple operation, low cost and rapid detection. The detection platform can also be extended to analyze the level of β-gal in other types of cells or biological samples. Overall, the simple, effective and dual-readout assay holds promise for efficient sensing of β-gal activity and provides a potential tool for E. coli detection and their antibiotic resistance analysis.

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Section: Introductionmentioning

confidence: 99%

An enzyme-activatable dual-readout probe for sensitive β-galactosidase sensing and Escherichia coli analysis

Huang

Feng

Zhang

et al. 2022

Front. Bioeng. Biotechnol.

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“…Alternatively, synthetic biomarkers (Fig. 2c ) that are designed to interact with biomolecules can be introduced into the body (for example, through injection) to indicate and amplify physiological conditions (for example, by reacting with an overexpressed enzyme) 22 , 23 . Synthetic biomarkers can have various configurations; however, all of them contain two essential components: a recognition region (for example, substrates 24 and promoter sequences 25 ) to target the biochemical process and a reporter region (for example, volatile organic compounds 24 and genes 25 ) to signal its presence.…”

Section: Strategies For Signal Amplificationmentioning

confidence: 99%

Biomolecular sensors for advanced physiological monitoring

et al. 2023

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Body-based biomolecular sensing systems, including wearable, implantable and consumable sensors allow comprehensive health-related monitoring. Glucose sensors have long dominated wearable bioanalysis applications owing to their robust continuous detection of glucose, which has not yet been achieved for other biomarkers. However, access to diverse biological fluids and the development of reagentless sensing approaches may enable the design of body-based sensing systems for various analytes. Importantly, enhancing the selectivity and sensitivity of biomolecular sensors is essential for biomarker detection in complex physiological conditions. In this Review, we discuss approaches for the signal amplification of biomolecular sensors, including techniques to overcome Debye and mass transport limitations, and selectivity improvement, such as the integration of artificial affinity recognition elements. We highlight reagentless sensing approaches that can enable sequential real-time measurements, for example, the implementation of thin-film transistors in wearable devices. In addition to sensor construction, careful consideration of physical, psychological and security concerns related to body-based sensor integration is required to ensure that the transition from the laboratory to the human body is as seamless as possible.

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“…One is an activity-based synthetic biomarker technique involving the administration of exogenous agents that interact with tumor tissue or its microenvironment to produce more concentrated molecular tumor biomarkers, and the other is a genetically encoded synthetic biomarker technique inducing the production or secretion of bioorthogonal reporters by resident or infiltrated cells within the tumor microenvironment. [64] Numerous works have demonstrated the generation of synthetic biomarkers detectable in blood plasma, [65] through breath, [66] and more frequently in urine. [67] For example, by administrating activity-based nanosensors into the airways of mice with lung tumors, concentrated small reporter molecules were released into the urine as detectable synthetic biomarkers, enabling early detection of lung cancer.…”

Section: Synthetic Biomarkersmentioning

confidence: 99%

“…Numerous works have demonstrated the generation of synthetic biomarkers detectable in blood plasma, [65] through breath, [66] and more frequently in urine [67] . For example, by administrating activity‐based nanosensors into the airways of mice with lung tumors, concentrated small reporter molecules were released into the urine as detectable synthetic biomarkers, enabling early detection of lung cancer [68] .…”

Section: Potential Cancer Biomarkers In Human Urinementioning

confidence: 99%

Microfluidics‐Based Urine Biopsy for Cancer Diagnosis: Recent Advances and Future Trends

2022

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Urine biopsy, allowing for the detection, analysis and monitoring of numerous cancer-associated urinary biomarkers to provide insights into cancer occurrence, progression and metastasis, has emerged as an attractive liquid biopsy strategy with enormous advantages over traditional tissue biopsy, such as non-invasiveness, large sample volume, and simple sampling operation. Microfluidics enables precise manipulation of fluids in a tiny chip and exhibits outstanding performance in urine biopsy owing to its minimization, low cost, high integration, high throughput and low sample consumption. Herein, we review recent advances in microfluidic techniques employed in urine biopsy for cancer detection. After briefly summarizing the major urinary biomarkers used for cancer diagnosis, we provide an overview of the typical microfluidic techniques utilized to develop urine biopsy devices. Some prospects along with the major challenges to be addressed for the future of microfluidicbased urine biopsy are also discussed.

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Beta-galactosidase-responsive synthetic biomarker for targeted tumor detection

Abstract: Tumor biomarkers are highly desirable for the screening of patients with a risk of tumor development and progression.

Cited by 9 publications

References 27 publications

An enzyme-activatable dual-readout probe for sensitive β-galactosidase sensing and Escherichia coli analysis

An enzyme-activatable dual-readout probe for sensitive β-galactosidase sensing and Escherichia coli analysis

Biomolecular sensors for advanced physiological monitoring

Microfluidics‐Based Urine Biopsy for Cancer Diagnosis: Recent Advances and Future Trends

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