Novel Near-infrared Fluorescent Probe For Tumor And Liver Injury Imaging

Cancer has become the most serious public health problem and the leading cause of death all over the world.Molecular imaging technologies play an irreplaceable role in the field of the prevention and cure of cancer including early screening,imaging-guided surgery and drug-induced liver injury detection.With weaker auto-fluorescence interference,lower biological tissue absorption and stronger tissue-penetrating ability,near-infrared fluorescence imaging has become a research hotspot in the field of molecular imaging during the recent years.Dicyanomethylene-benzopyran-based near-infrared fluorescent dyes have many excellent optical properties and wide range of potential applications.In this study,with the aid of the Gaussian calculation of molecular orbital energy level,the heteroatom substitution strategy was applied to the structural modification of this kind of dyes.Meanwhile,in order to facilitate conjugation with targeting peptide for bioimaging,a modifiable group was introduced into their structure.Finally,three novel near-infrared fluorescent dyes——9a,9b and 9c were successfully synthesized.By systematically researching their optical properties,we verified that heteroatom substitution can indeed improve their spectral properties.However,at the same time,with larger atomic radius,the fluorescence quantum yield decrease significantly.Furthermore,we found that the fluorescence of such kind of dyes can be quenched by water.By coupling 9a and CH1055 to a short peptide CREKA with the ability to target fibrinfibronectin complexs,which overexpressed in the liver injury and tumor sites,two watersoluble imaging probe 9a-CREKA and CH1055-CREKA were synthesized.In vitro experiments,the fluorescence intensity of 9a-CREKA in water was very weak,while its fluorescence intensity was dramatically enhanced when combined with the target protein.However,the fluorescence intensity of CH1055-CREKA almost cannot be influenced by this target protein,and in vivo imaging experiments,there was very strong fluorescence signal in the normal liver,so it is impossible to detect liver injury using this probe,but it still can be applied to imaging tumor with excellent result.Due to the fluorescence of 9aCREKA can be quenched by water and dramatically enhanced by target protein,this probe exhibit very weak signal in the normal liver,and have very excellent performance in the targeted imaging of liver injury and tumor.