Construction Of Tumortargeted Exosomes With Coloading Of Docetaxel And SiPLK1 And Their Anti-Prostate Cancer Effects

Prostate cancer is the most common malignancy in most Western countries.In recent years,with the aging of the country and the change of lifestyle,the incidence of prostate cancer in China has increased year by year.For castration-resistant advanced prostate cancer,the current treatment is mainly chemotherapy,and the treatment is very limited.The combination of chemotherapeutic drugs and gene drugs based on nanotechnology is a hot topic in current cancer treatment research.In this study,with the concept and technology of gene therapy and nano drug targeted delivery,macrophage-derived exosomes were used as drug carriers,and the first-line chemotherapy drug docetaxel and the gene drug siPLK1 were used to construct tumor-targeted exosomes co-loaded with docetaxel and the gene drug siPLK1.Its anti-prostate cancer effect was systematically evaluated in vitro and in vivo.The research content of the first chapter mainly includes three parts: 1.The stearoyl polypeptide micelles co-loaded with docetaxel and siPLK1 were constructed and characterized based on the intracellularly degradable stearoyl polypeptide polymer developed by the research group.2.The mouse macrophage cell line Raw264.7 was transfected with stearyl peptide micelles co-loaded with docetaxel and siPLK1,and the exosomes co-loaded with docetaxel and siPLK1 were directly produced by one-step method by active loading,and were isolated and purified;3.Using the lipophilic properties of the exosomal membrane,we connect DSPE-PEG-FA to the surface of the exosomes,and introduce a folate target and PEG that can target the epithelial-derived tumor,improving its function and targeting.we prepare Tumor-targeted exosomes co-loaded with docetaxel and siPLK1 and characterize them.The second chapter of the study examined the anti-prostate cancer cell proliferation of tumor-targeted exosomes(Co-Exo-FA)co-loaded with docetaxel and siPLK1 at the cell level in vitro,and elucidated its target for prostate cancer cells.The study also clarified the ability to inhibit the expression of PLK1 protein in cells and the synergistic effect of the combination of siPLK1 and DTX.The third chapter of the subject was evaluating in vivo by constructing a subcutaneous xenograft model of human prostate cancer in nude mice on the basis of previous evaluation in vitro.Through the research of the subject,a method for co-transfection of chemotherapeutic drugs and gene drugs to prepare exosomes for co-loading chemotherapy drugs and gene drugs was created.The tumor-targeted exosomes we constructed provide new ideas for the treatment of castration-resistant prostate cancer and other malignant tumors.