Preliminary Exploration Of Imaging And Treatment Of Glioma Based On Exosomes Derived From Glioma Tissue

Glioma is a common malignant tumor with a high fatality rate.At present,surgical resection combined with temozolomide chemotherapy is mainly used in clinical practice.However,temozolomide has poor water solubility and low bioavailability.Therefore,it is extremely important to develop a nanocarrier system that can improve the water solubility of temozolomide and target it to the tumor site.Compared with the common liposomes and polymeric nanoparticles,exosomes can not only be used as a carrier of tumor treatment drugs to improve the solubility and bioavailability of hydrophobic drugs but also because they are cell secretions and are biocompatible and able to actively cross the blood-brain barrier,which is conducive to the targeted therapy of glioma.At present,the source of exosomes is focused on extracting from tumor cells,but tumor cells and tumor tissues are essentially different.Compared with cell-derived exosomes,exosomes extracted from tumor tissues can reflect more tumor-related information.Therefore,this article is based on the exosomes extracted from the brain glioma tissue for the preliminary exploration of brain glioma imaging and treatment.The main research includes the following two aspects:(1)The identification of glioma tissue exosomes and the evaluation of tumor targeting ability.Transmission electron microscopy and particle size analyzer showed that the particle size of exosomes was in the range of 20～300 nm;Western blot experiments proved that the sucrose density gradient ultra-high-speed centrifugation method can successfully extract different layers of glioma tissue Source exosomes.The results of confocal imaging and flow cytometry showed that exosomes derived from glioma tissue can be taken up by GL261 tumor cells,U87 tumor cells,U251 tumor cells and 4T1 tumor cells,indicating that tissue-derived exosomes have no tumor Specificity.The in vivo optical imaging of DiI-labeled glioma tissue-derived exosomes(Exosome-DiI)on GL261,4T1 and other tumors further proves this conclusion.(2)Preliminary study on the ability of curcumin encapsulated in exosomes derived from glioma tissue to inhibit the growth of subcutaneous glioma.Different concentrations of Exosome-CUR have a concentration-dependent killing ability on tumor cells.When the concentration of Exosome-CUR is 20 μg/mL,the survival rate of tumor cells is significantly reduced.This killing ability is carried out by inducing cell apoptosis.Compared with PBS and exosomes alone treatment group,tail vein injection of Exosome-CUR(2 mg/Kg)can significantly inhibit the growth of subcutaneous glioma.In summary,this article successfully extracted exosomes from glioma tissue,and initially realized the in vivo fluorescence imaging and therapeutic application of glioma,laying the foundation for subsequent related research.