Application Research Of FAPI Organic Small Molecules For Tumor Targeting And Diagnosis And Treatment

Cancer is a serious threat to human life and health,but traditional therapeutic drugs have low tumor enrichment and poor therapeutic effect.Tumor-associated fibroblasts(CAFs)are widely present in various tumor tissues and play a role in promoting tumor growth,proliferation and metastasis.CAFs selectively and highly express fibroblast activation protein(FAP?)in tumor tissues,but rarely in other normal tissues.Therefore,targeting FAP? can increase the enrichment of tumor diagnosis and treatment reagents and improve the diagnosis and treatment effect.This paper used FAP? inhibitor(FAPI)as the targeting unit to explore its application in tumor diagnosis and treatment,as follows:Chapter 1: Synthesis of fluorescent probe FITC-FAPI and its application in tumor diagnosis.We have designed and synthesized FAPI targeting ligands and coupled fluorescein FITC to it to obtain small-molecule FITC-FAPI fluorescent probes.The probe not only specifically binds to FAP? and inhibits its enzymatic activity in solution,but also exhibits excellent fluorescence properties.Using the transplanted tumor mice as a model,it was proved that the FITC-FAPI probe can specifically target the tumor tissue with high FAP? expression,realize the imaging of tumor tissue,and can be used for the diagnosis of tumors with high FAP? expression.Chapter 2: Synthesis of FAPI-modified melphalan(MEL-FAPI)and evaluation of its efficacy.To improve the tumor enrichment rate of the chemotherapeutic drug MEL,we synthesized the targeted drug MEL-FAPI through covalent linkage of amide bonds.The experimental results demonstrated the successful coupling of FAPI and MEL.MEL-FAPI not only has better affinity for FAP?-expressing tumor cells,but also maintains high toxicity.Therefore,the successful preparation of this reagent provided a new idea for improving the therapeutic effect of MEL.This paper successfully synthesized a small molecule inhibitor(FAPI)targeting FAP?,and explored the targeting of its conjugated fluorescein and chemotherapeutic drugs,providing new ideas for tumor diagnosis and treatment.