Detection Of Cancer Biomarker MicroRNA By Lanthanide Fluorescence Nanoprobes

MicroRNAs(miRNAs)are a class of non-protein-coding,single-stranded,small(approximately 22 nucleotides)RNAs.It has been demonstrated that miRNAs play critical regulatory functions in many physiological processes,such as cell differentiation,proliferation and apoptosis.Aberrant expression of certain miRNAs is closely associated with various diseases,especially cancers.Currently,miRNA has become an emerging biomarker for cancer prognosis,diagnosis and therapy.Note that most of the detection methods for miRNA are based on enzyme-based amplification where specific reaction conditions are needed.What's more,the autofluorescence from biological samples deteriorates the detection sensitivity.Thus,there remains great challenge when these conventional amplification methods are applied to complex system like serum.To overcome these drawbacks,we have developed the first inorganic lanthanide(Ln3+)nanoprobe coupled with molecular beacon(MB)for the detection of cancer biomarker miRNA-21.The proposed strategy by employing the long-lived luminescence of Ln3+,which brings together the advantage of fluorescence amplification of Ln3+ in the enhancer solution and near-zero background signal from the time-resolved technique,provides a new strategy to ultrasensitive detection of miRNA-21.The assay exhibited a linear dynamic range spanning from 10 fM to 100 pM along with an detection limit down to 1.38 fM,which is 3 orders of magnitude lower than that of the conventional fluorescent probe.Meanwhile,the developed biosensor showed high specificity that was capable of distinguishing even single-nucleotide mutation miRNA sequence,due to the excellent selectivity of MB.Particularly,miRNA-21 spiked in fetal bovine serum was successfully detected with the recovery in the range of 90.2-108.3%and coefficients of variation below 10.1%,indicating its promising applications in RNA immunoassay and early cancer diagnosis.