Recently, Professor Gui Shuangying, Researcher Cheng Zhifei, and Associate Researcher Wang Qi from the School of Pharmacy at Anhui University of Traditional Chinese Medicine formed a joint team to propose a new strategy for the comprehensive treatment of Parkinson's disease, which involves blocking the source of neuroinflammation caused by microglia from the "inside" and preventing the continuous infiltration of peripheral immune cells from the "outside" to regulate immune system function. The relevant research paper was recently published in the international academic journal ACS Nano. Previous studies have focused more on suppressing inflammation in the brain. Wang Qi told Science and Technology Daily reporters that Parkinson's disease is one of the most common neurodegenerative diseases, and its pathogenesis is roughly the abnormal aggregation of alpha synuclein in dopaminergic neurons in the substantia nigra of the midbrain, which triggers a cascade of neuroinflammation and blocks the normal secretion of dopamine by neurons. Reduced dopamine levels can lead to abnormal brain activity and trigger symptoms such as movement disorders. The academic community believes that neuroinflammation is a key factor leading to abnormal accumulation of alpha synuclein, reduced dopamine secretion, and neuronal failure. Therefore, the research team focuses on studying the regulation of neuroinflammation. At present, drug therapy is mainly used in clinical practice to regulate neuroinflammation in Parkinson's disease. Drugs used include antibody drugs that target the abnormal aggregation of alpha synuclein, drugs that increase dopamine levels, neuroprotective drugs, and anti-inflammatory drugs. In addition, the overactivated brain immune microenvironment is a key factor in the rapid development of Parkinson's disease. To address the neuroinflammation caused by overactivated microglia in the brain, there are currently treatment strategies such as activating downstream anti-inflammatory signaling pathways and using nanoenzyme biocatalysis to clear free radicals in the brain. However, if we only suppress neuroinflammation in the brain without timely blocking and curbing the immune deterioration caused by peripheral immune cell infiltration, it will be difficult to effectively treat Parkinson's disease. The research team proposed a comprehensive and collaborative treatment strategy of "internal and external cultivation" to reshape the overactivated immune microenvironment of Parkinson's disease. Engineering extracellular vesicles have dual functions. Wang Qi introduced that human cells will continue to secrete extracellular vesicles. These vesicles play a crucial role in the transmission of genetic material and functional components between cells, with the potential to serve as drug delivery carriers, disease diagnostic markers, and potential therapeutic tools. However, the function of extracellular vesicles is limited by the mother cell and difficult to use for the treatment of complex diseases. In response, the research team utilized bio nanotechnology to engineer extracellular vesicles to meet the treatment needs of Parkinson's disease. The research team utilized gene editing technology to obtain an extracellular vesicle with special functions. This type of vesicle can actively search for and identify the lesion area. The chemokine receptor CCR2 expressed on the surface of vesicles can monitor and bind to a specific chemokine in the lesion area, blocking the entry of inflammatory cells into the lesion area dependent on this factor. Next, the research team used the active ingredient dihydrotanshinone I from traditional Chinese medicine Danshen as a highly effective anti-inflammatory agent to prepare dihydrotanshinone I nanoparticles. Through membrane encapsulation technology, the team successfully prepared engineered extracellular vesicles by encapsulating specially functional extracellular vesicles around dihydrotanshinone I nanoparticles. Wang Qi gave a vivid example. If we compare the overactivated immune microenvironment of Parkinson's disease to a castle occupied by the enemy, we need to start from two aspects to eliminate the enemy: one is to eliminate internal enemies; The second is to tightly seal the city gates to prevent external enemies from invading again. At present, most research only focuses on eliminating internal "enemies", that is, using methods such as activating anti-inflammatory pathways or biocatalysis to suppress neuroinflammation. In contrast, the research team has adopted a new strategy that can use extracellular vesicles with special functions to accurately locate and close the "city gate" in the human body; At the same time, enter the "castle" and use the traditional Chinese medicine ingredient dihydrotanshinone I to efficiently eliminate internal "enemies" and synergistically treat Parkinson's disease in multiple ways. Gui Shuangying told reporters that this new strategy can control inflammation in the lesion area while avoiding the invasion of external pro-inflammatory cells, providing new ideas for the clinical treatment and drug development of Parkinson's disease in the future. Although the team has designed and selected substrates with good biocompatibility and low immunogenicity for the development of engineered extracellular vesicles, there are still challenges in practical clinical applications, such as high production costs, difficulty in mass production, and potential biosafety hazards. Wang Qi said, "The team will combine the advantages of traditional Chinese medicine platform at Anhui University of Traditional Chinese Medicine to further develop low-cost, easy to obtain, safe and stable efficacy herbal derived extracellular vesicles, overcoming the challenges of clinical application