Peroxynitrite (ONOO) plays important roles in the progression of important disease such as inflammation, cancer, and diabetes, which made it an attractable target for biosensor development. However, to detect ONOO solely is highly dependent on the sensitivity of the detection method and may be disturbed by unwillingly false-positive signal. Cellular viscosity is an important microenvironmental parameter and its abnormal changes are closely related to diseases such as diabetes and cancer. In this case, to construct a "dual-locked" molecular tool for both ONOO and viscosity sensing and to evaluate the performance of such strategy in disease diagnosis is of great importance. We herein firstly reported the construction of a novel "dual-locked" probe DCI-OV which showed capability for simultaneous measuring ONOO concentration and system viscosity with high sensitivity (LOD = 4.7 nM) and high specificity. Moreover, both exogenous and low level of endogenous ONOO in living cells could be detected using DCI-OV due to viscosity amplified signal. Furthermore, cancer cells and insulin-resistant cells could be easily distinguished using DCI-OV. By taking advantage of the "dual-locked" sensing strategy, a total of 85 samples of human serum were screened using DCI-OV based rapid disease screening method and it was capable of differentiated and subdivided patients into specific type of disease, indicating the great potential of application of DCI-OV into clinical related disease diagnosis.
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