Engineered Exosomes with Independent Module/Cascading Function for Therapy of Parkinson's Disease by Multistep Targeting and Multistage Intervention Method.

Current exosome engineering methods usually lead to the damage of exosome morphology and membrane, which cannot meet the complex needs of disease treatment. Herein, the concept of an "independent module/cascading function" is proposed to construct an engineered exosome nanotherapy platform including an independent artificial module and a natural module. The artificial module with movement/chemotaxis function is first synthesized, and then it is controllably combined with the natural exosome module with "one by one" mode through a "differentiated" modification method. The whole process can not only maintain the activity of the natural exosome module, but also endows it with motion ability, so as to realize the purpose of "cascading function" in the process of disease treatment. The above engineered exosomes are used in the treatment of Parkinson's disease (PD). Moreover, the multistep targeting strategy of "disease microenvironment-damaged cells-diseased mitochondria" and the multistage intervention concept of "inhibiting deterioration and promoting repair" are proposed, so as to break through the bottleneck of the existing treatment of PD.