pH-Tunable Oxidase-Like Activity of Cerium Oxide Nanoparticles Achieving Sensitive Fluorigenic Detection of Cancer Biomarkers at Neutral pH

    Authors

    A. Asati; C. Kaittanis; S. Santra;J. M. Perez

    Comments

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    Abbreviated Journal Title

    Anal. Chem.

    Keywords

    BREAST-CANCER; ULTRASENSITIVE DETECTION; CELLS; IMMUNOSENSOR; DERIVATIVES; PROTEINS; Chemistry, Analytical

    Abstract

    The reliable and sensitive detection of cancer-specific biomarkers is important for the diagnosis and treatment of cancer. Hence, detection of these biomarkers has to be reliably and rapidly Performed in diverse settings. A limitation of the conventional biomarker-screening method of enzyme-linked immunosorbent assay (ELISA) is the employment of labile components, such as hydrogen peroxide and horseradish peroxidase. Previously, we reported that nanoceria is able to oxidize various colorimertic dyes at acidic pH, such as 3,3',5,5'-tetramethylbenzydine (TMB) and 2,2-azinobis-(3-ethylbenzothizoline-6-sulfonic acid) (AzBTS), and an assay was designed for screening the folate receptor. Herein, we show that the ability of nanoceria to oxidize a substrate can be tuned by modulating the pH. Results showed that nanoceria can oxidize the nonfluorescent substrate ampliflu, either to the very stable fluorescent product resorufin at pH 7.0 or to the nonfluorescent resazurin at pH 4.0. On the basis of these findings, we conjugated Protein G to immobilize antibodies on the surface of nanoceria, in order to detect the expression of prototypic cancer biomarkers at pH 7.0, such as the folate receptor and EpCAM. We found that within 3 h, nanoceria identified the expression of the folate receptor and EpCAM on lung carcinoma and breast adenocarcinoma cells, respectively. Traditional ELISA had a readout time of 15 h and a higher detection threshold, while requiring multiple washing steps. Considering these results and nanoceria's ability to oxidize ampliflu to its stable fluorescent product at neutral pH, the use of antibody-carrying nanoceria in the lab and point-of-care molecular diagnostics is anticipated.

    Journal Title

    Analytical Chemistry

    Volume

    83

    Issue/Number

    7

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    2547

    Last Page

    2553

    WOS Identifier

    WOS:000288887700022

    ISSN

    0003-2700

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