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Ultrasensitive Point-of-Care Test for Tumor Marker in Human Saliva Based on Luminescence-Amplification Strategy of Lanthanide Nanoprobes.

ABSTRACT: The point-of-care detection of tumor markers in saliva with high sensitivity and specificity remains a daunting challenge in biomedical research and clinical applications. Herein, a facile and ultrasensitive detection of tumor marker in saliva based on luminescence-amplification strategy of lanthanide nanoprobes is proposed. Eu₂O₃ nanocrystals are employed as bioprobes, which can be easily dissolved in acidic enhancer solution and transform into a large number of highly luminescent Eu³⁺ micelles. Meanwhile, disposable syringe filter equipped with nitrocellulose membrane is used as bioassay platform, which facilitates the accomplishment of detection process within 10 min. The rational integration of dissolution enhanced luminescent bioassay strategy and miniaturized detection device enables the unique lab-in-syringe assay of tumor marker like carcinoembryonic antigen (CEA, an important tumor marker in clinic diagnosis and prognosis of cancer) with a detection limit down to 1.47 pg mL^-1 (7.35 × 10^-15 m). Upon illumination with a portable UV flashlight, the photoluminescence intensity change above 0.1 ng mL^-1 (0.5 × 10^-12 m) of CEA can be visually detected by naked eyes, which allows one to qualitatively evaluate the CEA level. Moreover, we confirm the reliability of using the amplified luminescence of Eu₂O₃ nanoprobes for direct quantitation of CEA in patient saliva samples, thus validates the practicality of the proposed strategy for both clinical diagnosis and home self-monitoring of tumor marker in human saliva.

SUBMITTER: Zhou S

PROVIDER: S-EPMC7927602 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Ultrasensitive Point-of-Care Test for Tumor Marker in Human Saliva Based on Luminescence-Amplification Strategy of Lanthanide Nanoprobes.

Zhou Shanyong S Tu Datao D Liu Yan Y You Wenwu W Zhang Yunqin Y Zheng Wei W Chen Xueyuan X

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20210106 5

The point-of-care detection of tumor markers in saliva with high sensitivity and specificity remains a daunting challenge in biomedical research and clinical applications. Herein, a facile and ultrasensitive detection of tumor marker in saliva based on luminescence-amplification strategy of lanthanide nanoprobes is proposed. Eu<sub>2</sub>O<sub>3</sub> nanocrystals are employed as bioprobes, which can be easily dissolved in acidic enhancer solution and transform into a large number of highly lum ...[more]

PMID: 33717839

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Project description:Ligand-sensitized, luminescent lanthanide(III) complexes are of considerable importance because their unique photophysical properties (microsecond to millisecond lifetimes, characteristic and narrow emission bands, and large Stokes shifts) make them well suited as labels in fluorescence-based bioassays. The long-lived emission of lanthanide(III) cations can be temporally resolved from scattered light and background fluorescence to vastly enhance measurement sensitivity. One challenge in this field is the design of sensitizing ligands that provide highly emissive complexes with sufficient stability and aqueous solubility for practical applications. In this Account, we give an overview of some of the general properties of the trivalent lanthanides and follow with a summary of advances made in our laboratory in the development of highly luminescent Tb(III) and Eu(III) complexes for applications in biotechnology. A focus of our research has been the optimization of these compounds as potential commercial agents for use in homogeneous time-resolved fluorescence (HTRF) technology. Our approach involves developing high-stability octadentate Tb(III) and Eu(III) complexes that rely on all-oxygen donor atoms and using multichromophore chelates to increase molar absorptivity; earlier examples utilized a single pendant chromophore (that is, a single "antenna"). Ligands based on 2-hydroxyisophthalamide (IAM) provide exceptionally emissive Tb(III) complexes with quantum yield values up to approximately 60% that are stable at the nanomolar concentrations required for commercial assays. Through synthetic modification of the IAM chromophore and time-dependent density functional theory (TD-DFT) calculations, we have developed a method to predict absorption and emission properties of these chromophores as a tool to guide ligand design. Additionally, we have investigated chiral IAM ligands that yield Tb(III) complexes possessing both high quantum yield values and strong circularly polarized luminescence (CPL) activity. To efficiently sensitize Eu(III) emission, we have used the 1-hydroxypyridin-2-one (1,2-HOPO) chelate to create remarkable ligands that combine excellent photophysical properties and exceptional aqueous stabilities. A more complete understanding of this chromophore has been achieved by combining low-temperature phosphorescence measurements with the same TD-DFT approach used with the IAM system. Eu(III) complexes with strong CPL activity have also been obtained with chiral 1,2-HOPO ligands. We have also undertaken kinetic analysis of radiative and nonradiative decay pathways for a series of Eu(III) complexes; the importance of the metal ion symmetry on the ensuing photophysical properties is clear. Lastly, we describe a Tb(III)-IAM compound--now carried through to commercial availability--that offers improved performance in the common HTRF platform and has the potential to vastly improve sensitivity.

Dataset Information

Ultrasensitive Point-of-Care Test for Tumor Marker in Human Saliva Based on Luminescence-Amplification Strategy of Lanthanide Nanoprobes.

Publications

Ultrasensitive Point-of-Care Test for Tumor Marker in Human Saliva Based on Luminescence-Amplification Strategy of Lanthanide Nanoprobes.

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