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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.

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