外泌体在药物递送方面越来越显示出巨大的应用潜力。然而，如何获得大量均一、稳定、多组分可控的外泌体是当前亟待解决的问题。本课题创新性的利用天然海洋单细胞藻类进行外泌体的制备研究，同时借助外泌体在药物递送方面的天然优势，利用食管癌细胞表面高表达HER2这一特性，构建高表达靶向食管癌特异性结合肽的外泌体递送系统，然后装载治疗性miR-375、偶联anti-PDL1，以实现靶向食管肿瘤的递送和联合治疗。通过进一步研究盐藻外泌体的发生、T-HER2短肽修饰及miR-375/anti-PDL1的装载/释放，揭示其与食管癌细胞识别、相互作用及胞内输运的一般规律，解决其体外靶向性的问题；进一步在小鼠食管癌模型上考察其靶向递送能力和微环境抑瘤的机理。本研究有望成功制备出高表达靶向肿瘤的外泌体递送系统，解决当前外泌体制备的技术瓶颈，同时，该方法有望应用于其他疾病的靶向递送体系，具有重要的理论意义和应用价值。

Exosomes are increasingly showing its great potential in the field of drug delivery. However, it is the current urgent problem to be solved how to obtain a large number of multi-component controllable exosomes with uniform and stable. In this project, we use of natural Marine single-celled algae for the preparation of exosomes, based on the natural advantages of exosome in terms of drug delivery, using the feature of high expressionof HER2 in esophageal cancer cell surface, to construct a delivery system based on exosome with targeting peptides. Then loading therapeutic miR-375, coupling anti-PDL1 to the exosome, achieving the targeted delivery to esophageal cancer cell and synergistic therapy. we would reveal the mechanisms of the cargoes loaded exosome's recognition and interaction with the esophageal cancer cells, as well as the general rules of the transport in the receptor cells, and solve the targeting of exosome in vitro by investigating the secretion and T-HER2 peptide modification of Dunaliella-derived exosomes, loading/releasing mechanisms of miR-375/anti-PDL1 antibody. And then, in the mouse intracranial esophageal cancer model, we will examine the targeted delivery and therapeutic efficacy of the cargoes loaded exosome to esophageal tumor. Moreover, the further mechanisms of its microenvironmental antitumor on the esophageal toumor will be investigated. This project is expected to successfully prepare a delivery system with high expressed of tumor targeting exosomes, and solve the technical bottlenecks in preparation of a large number of exosome with uniform, stable, controllable components. this method can also be applied in other disease targeting delivery system, which has important theoretical significance and application value.