Title

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

Authors

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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