Construction Of Cysteine-Activated NIR Fluorescence/Photoacoustic Imaging Probe And Their Biological Applications

As an important biological thiol,cysteine（Cys）plays a crucial role in basic physiological processes,such as the protein biosynthesis,enzyme active sites and redox balance regulations.Thus,constructing a series of molecular imaging probes with high sensitivity for quantitative detection and visualization of Cys in vitro and in vivo,is of great significance for studying the role of Cys in human physiology and pathology.Moreover,activatable NIR imaging probes have received tremendous attention in detection and bioimaging due to their outstanding advantages such as strong tissue penetration,high signal-to-background ratio,high sensitivity,and specificity.Herein,a series of activatable imaging probes with NIR absorption and emission wavelength were constructed based on the highly tunable platform of hemicyanine derivatives.Furthermore,these activatable imaging probes were applied in monitoring and FL/PA imaging the Cys level in living cells and disease models in mice.As follows:（1）In Chapter 2,an activatable NIR PA probe NITy with long absorption wavelength（λ=800 nm）was constructed.After the probe specifically recognized Cys,a strong PA signal at 800 nm in NIR region was activated.It was notable that the activatable PA probe was successfully applied for real-time PA imaging of exogenous and endogenous Cys in living mouse.This probe provides an effective PA imaging tool for real-time visualization of Cys related physiological process.（2）In Chapter 3,an activatable water-soluble PA probe NCTy was constructed based on the heteroatom substitution theory.After the probe specifically recognized Cys,a strong PA signal at 695 nm in NIR region was activated.More importantly,the activatable water-soluble PA probe was successfully applied for real-time PA imaging of overexpressed Cys in a tumor mouse model,for the first time.This probe provides a PA imaging tool with great development potential for real-time monitoring the process of tumor diagnosis and therapy.（3）In Chapter 4,an activatable NIR probe NKTy with significant FL and PA signal changes was constructed.After the probe specifically recognized Cys,the FL₈₁₇ and PA₇₇₈ signals in NIR region were activated.Notably,the activatable probe was successfully applied to detect the Cys level in LPS-induced inflammation mouse model by FL and PA dual-modality imaging method,for the first time.This probe provides a new imaging tool for monitoring the level of Cys in inflammation.