Theranostics 2018; 8(13):3461-3473. doi:10.7150/thno.25179

Research Paper

“Three-in-one” Nanohybrids as Synergistic Nanoquenchers to Enhance No-Wash Fluorescence Biosensors for Ratiometric Detection of Cancer Biomarkers

Xiaolin Huang1,2#, Zhimei He3,2#, Dan Guo3, Yijing Liu2, Jibin Song2, Bryant C. Yung2, Lisen Lin2, Guocan Yu2, Jun-Jie Zhu3✉, Yonghua Xiong1✉, Xiaoyuan Chen2✉

1. State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, P. R. China
2. Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland 20892, United States
3. State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China
#These authors contributed equally to this work.


Purpose: Early diagnosis of cancer enables extended survival and reduced symptoms. To this end, a “three-in-one” nanohybrid of MOF@AuNP@GO is designed as synergistic nanoquencher to develop a novel fluorescence biosensor for rapid and sensitive detection of cancer-related biomarkers.

Methods: The ssDNA absorption affinities and fluorescence quenching abilities of the MOF@AuNP@GO were evaluated using FAM-labeled single-stranded DNA (ssDNA). Then, two specific dye-labeled ssDNA and aptamer probes were designed for the recognition of p53 gene and prostate specific antigen (PSA), respectively. Fluorescence spectra were recorded and ratiometric signal processing was performed.

Results: The designed nanohybrids exhibit enhanced ssDNA binding affinities and fluorescence quenching abilities, which significantly decrease the background signal and increase the signal-to-noise (S/N) ratio, thus lowering the detection limit (LOD). Accordingly, with ratiometric measurement, this developed nanosensor can sensitively measure p53 gene and PSA with LODs of 0.005 nM and 0.01 ng mL-1, respectively. Besides, this method also displays excellent performances with respect to universality, multiplexed detection, specificity, and practicality in human serum.

Conclusion: The designed MOF@AuNP@GO-based fluorescence biosensor can serve as a promising platform for washing-free, rapid and sensitive measurement of cancer biomarkers, making this method well-suited for point-of-care (POC) diagnosis.

Keywords: nanohybrid, nanoquencher, fluorescence, no-wash biosensor, ratiometric, cancer biomarker

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
How to cite this article:
Huang X, He Z, Guo D, Liu Y, Song J, Yung BC, Lin L, Yu G, Zhu JJ, Xiong Y, Chen X. “Three-in-one” Nanohybrids as Synergistic Nanoquenchers to Enhance No-Wash Fluorescence Biosensors for Ratiometric Detection of Cancer Biomarkers. Theranostics 2018; 8(13):3461-3473. doi:10.7150/thno.25179. Available from