The Construction Of Fluorescent Nanoprobes Based On ZIF Materials And Thier Aapplication In Cancer Imaging

Today,cancer is still one of the biggest public enemies of global health with its high morbidity and mortality.Achieving early diagnosis is the most effective means of reducing cancer harm,which requires the use of powerful tools to accurately identify biomarkers in the complex cancer microenvironment.Therefore,the construction of fluorescent nanoprobes with excellent performance for the correlation detection of various cancer markers is of great significance for early cancer diagnosis.In this paper,three fluorescent nanoprobes were constructed and realized near-infrared（NIR）fluorescence detection or sequential detection of three important cancer markers（ATP,ONOO^-and SO₂）,and successfully applied to cancer imaging.1.Firstly,three fluorescent nanoprobes based on ZIF-90 and NIR dyes were constructed to detect ATP,and the nanoprobe CP@ZIF-90 with the best fluorescence property was selected from them.After the reaction of CP@ZIF-90 with ATP,the fluorescence at 705 nm is enhanced by 32 times,with high sensitivity,selectivity,and wonderful chemical stability.It is worth to point that carboxyl group in fluorescent dyes plays the important role,which provides a direction for the construction of NIR fluorescent nanoprobes based on ZIF-90.CP@ZIF-90 has good biocompatibility and the ability to enrich in tumor.It has been applied to the fluorescence monitoring of ATP in live cells（293T and CT26 cells）and mice.More importantly,CP@ZIF-90has shown great potential in distinguishing normal mice from tumor mice.2.Based on the previous single-analyte nanoprobe,a fluorescent nanoprobe which can sequentially detect two cancer markers was further developed to achieve more accurate cancer diagnosis.Herein,a fluorescent nanoprobe CPQ@ZIF-90 was constructed by encapsulating the ONOO^-sensitive unit CPQ in ZIF-90 through a self-assembly strategy for sequential detection of ATP and ONOO^-.The nanoprobe first reacts with ATP to release red fluorescence at 740 nm,and then shows high sensitivity and selectivity for the detection of ONOO^-,which enhances the green fluorescence.CPQ@ZIF-90 has good biocompatibility and has been successfully applied to the dual-channel sequential fluorescence detection of ATP and ONOO^-in living cells and zebrafish.Moreover,CPQ@ZIF-90 has been successfully applied to the fluorescence monitoring of ATP and ONOO^-in tumor-bearing mice,and has good performance in distinguishing normal from tumor mice.3.A fluorescent nanoprobe CPH@ZIF-90 was constructed by encapsulating the SO₂-sensitive unit CPH in ZIF-90 for sequential detection of ATP and SO₂.Firstly,the nanoprobe has high sensitivity,good selectivity and excellent stability for the detection of ATP,which enhances the fluorescence at 685 nm by 48 times.Subsequently,the released CPH also shows high sensitivity,ideal selectivity and fast response for the detection of SO₂.In addition,CPH@ZIF-90 has been successfully used for the sequential detection of endogenous ATP and SO₂ in living cells,and the distinction between normal cells and cancer cells.