NIR-? Small Organic Molecule Fluorophores For Surgical Navigation And Photothermal Therapy Of Tumor

In recent years,near-infrared ?(NIR-?,1000-1700 nm)fluorescence imaging has developed rapidly due to its higher imaging depth and excellent resolution compared with visible light(400-700 nm)and near-infrared I(NIR-I,700-900 nm)fluorescence imaging.In the past five years,a great number of near-infrared ? fluorescent probes of organic small molecules have been prepared for near-infrared ? biomedical imaging.As a result,they have excellent biocompatibility,rapid excretion and other advantages.Therefore,organic small-molecule NIR-? probes are one of the most promising candidates for future clinical applications.Herein,a PET/NIR-? dual-modality probe composed of a NIR-? organic small molecule with excellent tumor targeting ability was prepared by thiol-based click chemistry.Subsequently,the PET and NIR-? dual-modality tumor imaging and NIR-? image-guided tumor surgical navigation using this outstanding dual-mode probe was further explored.Moreover,through the electrostatic non-covalent interaction between sulfonate and cetuximab protein,a theranostic agent composed of a NIR-? organic small molecule was prepared,which had remarkable tumor-targeted imaging and photothermal therapy effect for colon cancer in in vivo and in vitro.The main contents of the thesis are as follows.Firstly,a PET/NIR-? dual-modality probe with integrin ?v?3 targeting function based on thiol-yne click chemistry was constructed for tumor delineation and image-guided surgery of gliomas.In this study,we have developed a novel,simple and effective strategy using base-catalyze thiol-yne click to prepare a NIR-?/PET dual-modal probe(⁶⁸Ga-CHS2)with high chemo-selectivity.This probe contains targeting peptide RGD,which target integrin ?v?3 receptors.In addition,⁶⁸Ga-CHS2 has a highly selective targeting ability for U87MG tumor cells that overexpress ?v?3 integrin receptors.The evaluations of PET/NIR-? imaging and image-guided surgery were performed in the nude mice bearing U87MG xenografts.Excellent PET/NIR-? dual-modality imaging qualities,high tumor uptake,high tumor and normal tissue contrast ratio,precise tumor delineation,and accurate NIR-? image-guided tumor surgery were successfully achieved in the tumor mice model.Secondly,the sulfonate modified NIR-? organic dye-Cetuximab complex is used in the study of NIR-? image-guided tumor photothermal therapy.In this study,a simple and feasible organic synthesis method in three steps was used to prepare the hydrophobic NIR-? dye H2a.After removing of trimethylsilyl alcohol protecting group of H2a,taurine was introduced into the NIR-? fluorophores by amide condensation reaction to obtain a water-soluble compound H2a-4T.Then,H2a-4T and fetal bovine serum(FBS)or the Ig G1 monoclonal antibody cetuximab that targeted the epidermal growth factor receptor(EGFR)were simply mixed to prepare H2a-4T@FBS or H2a-4T@Cetuximab complex.H2a-4T@FBS complex can be used for mouse lymph nodes NIR-? imaging,image-guided lymph node dissection.Furthermore,H2a-4T@Cetuximab complex has a very high photothermal conversion efficiency,can be used for in vivo NIR-? targeting imaging of HCT 116 colon cancer with EGFR over-expression and NIR-? image-guided tumor photothermal therapy.The tumor of the photothermal treatment group using H2a-4T@Cetuximab complex combined with laser irradiation is completely ablation.