ONOO~- Activated Near-infrared Fluorescent Probe For One/Two-photon Dual Mode In Vivo Imaging Of Tumor

A malignant tumor remains one of the leading causes of deaths across the world,because there are no obvious symptoms in the early stage of cancer,the current diagnosis method can only be used in the late stage of cancer.Thus,diagnosis of tumor development with noninvasive visualizing methods is significant for tumor therapy.Peroxynitrite(ONOO~-)is an important reactive nitrogen species in organisms,which plays an active role in signal transduction via nitrating tyrosine residues and immunogenic response against pathogen invasion,the excessive production of ONOO~-can induce cell death and organ injury.While in tumor microenvironment,the level of peroxynitrite and other active species are overexpressed.Molecular fluorescence imaging technique have been widely used for both analytical sensing and bioimaging owning to its high selectivity and sensitivity,easy operation,high resolution,real-time and non-invasive detection.Herein,an activatable two-photon NIR fluorescent probe DHQ-Rd-PN for in vivo imaging of peroxynitrite in a tumor was elaborately designed.The probe demonstrated an increased NIR emission in response to peroxynitrite in vitro,which ensured that the probe detects ONOO~-in cell and in vivo.Cellular imaging results disclosed that the probe was competent to detect adscititious ONOO~-level change in He La cells,as well as endogenous ONOO~-concentration in lipopolysaccharides(LPS)and IFN-γ-stimulated RAW 264.7 cells.Additionally,zebrafish in vivo imaging revealed that the probe accumulated in the pancreas and was lightened up by the addition of ONOO~-.Remarkably,the probe can be harnessed to image an ONOO~-production profile in xenograft 4T1 tumor mice by both one-photon and two-photon in vivo fluorescence imaging.Benefiting with the two-photon excitable properties and NIR emissive properties,the probe can be used for noninvasive in vivo imaging of ONOO~-in the onset and development of tumors for the first time.This work provided a noninvasive and efficient detection method for ONOO~-in a tumor,which would find more applications in tumor diagnosis and therapies.