Design,Preparation And Characterization Of Novel Fluorescent Glycocalix[4]arene For Glucose Transporter Mediated Bioimaging And Targeted Cisplatin Delivery

Fluorescence imaging technology is one of the most extensive and powerful visualization technologies in biological research and clinical diagnosis,with selectivity,visibility and adjustability.With the diversification of fluorescent probes and the improvement of related instruments,fluorescence imaging technology has been widely used in tumor imaging.Targeted fluorescent probes can specifically illuminate diseased cells and increase the detection rate of early cancer.With its unique cavity structure,the macrocyclic host molecule provides an important model for some complex structures and processes in the organism.Connecting sugars to various macrocyclic host molecules can not only prepare a variety of novel glycosyl conjugates.,And provide new action sites for macrocyclic molecules,enrich their functionality,and at the same time improve the limitations of macrocyclic molecules in certain applications.This topic is based on the tumor Warburg effect.Since tumor cells specifically express the sugar transport channel protein GLUT compared with healthy cells,GLUT1 is used as a tumor-specific marker to achieve targeted tumor recognition.The lower edge of the calixarene was derivatized with glucose,mannose and galactose,and a fluorescent group was introduced at the same time.The calixarene was designed,synthesized and characterized by a series of new nitrobenzofuran（NBD）labeled calixarene aromatic fluorescent probe（NBD-Gly-CA）.All the important intermediates and final products in the synthesis have been structurally confirmed by ¹H NMR,¹³C NMR and high-resolution mass spectrometry.At the same time,the cytotoxicity test proved that the probe is non-toxic,has a targeting ability to GLUT1 and can be positioned and imaged in tumor cells.The innovations of this subject are:（1）Using the Warburg effect of tumor cells,it can be directly used in cell lines to analyze and detect the expression level of GLUT protein in tumor cells,thereby completing the screening of tumor cells.It provides effective means and useful tools for the early screening and diagnosis of tumors,the discovery and development of new anti-tumor drugs,the prediction and evaluation of tumor resistance to chemotherapeutic drugs,and the treatment of tumor patients with high expression of GLUT protein.（2）Using calixarene as a structural platform,introducing different fluorophores to enable fluorescence imaging in tumor cells to achieve the role of positioning tumor cells.（3）Utilizing the ability of the sugar calixarene compound to contain different drugs in the cavity,the platinum drugs are encapsulated in the calixarene cavity to improve the solubility and anti-cancer activity of the platinum drugs.In short,the new calixarene probe designed and synthesized in this subject realizes the targeted imaging and screening of tumor cells,and provides a certain scientific basis for the design and development of a new calixarene fluorescent probe targeting the Warburg effect.