Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 11, Issue 20, Pages 18145-18152Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b02953
Keywords
circulating tumor DNA (ctDNA); surface-enhanced Raman scattering (SERS); frequency shift; RNase; DNA nanostructures
Funding
- National Natural Science Foundation of China [21621004, 31671012, 21575101, 21622404]
- National Basic Research Program of China [2015CB932004]
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Circulating tumor DNA (ctDNA) is a promising noninvasive biomarker for the early diagnosis of cancers. However, it is challenging for accurate and sensitive detection of pico-to-femtomolar serum concentration of ctDNA, especially in the presence of its analogues that produce strong background noise. Herein, a DNA-rN1-DNA-mediated surface-enhanced Raman scattering frequency shift assay is developed, which enables sensitive detection of ctDNA with one single base pair mutation (KARS G12D mutation) from the normal ones (KARS G12D normal) of lung cancer. This sensing platform features in both the designed hairpin DNA-rN1-DNA probe for specific ctDNA recognition and the employed RNase HII enzyme that specifically hydrolyzes the DNA-rN1-DNA/ctDNA hybrid and thus allows ctDNA recycling in the system to realize signal amplification. The detection system shows sub-femtomolar-level sensitivity in the phosphate-buffered saline solution and is demonstrated to function well in both fetal bovine serum and human physiological media. In particular, the sensitive assay of ctDNA in serum samples from lung cancer patients is achieved, suggesting its high potential applications in clinical settings for early diagnosis and prognosis of lung cancer.
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