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Due to the presence of the blood\u2010brain barrier (BBB), most small molecule drugs are difficult to reach the brain, leading to undesirable therapeutic outcomes. Recently, nanomedicines that can cross the BBB and precisely target lesion sites have emerged as thrilling tools to enhance the early diagnosis and treat various intractable brain disorders. Extensive research has shown that reactive oxygen species (ROS) play a crucial role in the occurrence and progression of brain diseases, including brain tumors and neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease, stroke, or traumatic brain injury, making ROS a potential therapeutic target. In this review, on the structure and function of BBB as well as the mechanisms are first elaborated through which nanomedicine traverses it. Then, recent studies on ROS production are summarized\u00a0through photodynamic therapy (PDT), chemodynamic therapy (CDT), and sonodynamic therapy (SDT) for treating brain tumors, and ROS depletion for treating NDDs. This provides valuable guidance for the future design of ROS\u2010targeted nanomedicines for brain disease treatment. The ongoing challenges and future perspectives in developing nanomedicine\u2010based ROS management for brain diseases are also discussed and outlined.<\/jats:p>","DOI":"10.1002\/smll.202410031","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T07:21:58Z","timestamp":1734333718000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["ROS Regulation in CNS Disorder Therapy: Unveiling the Dual Roles of Nanomedicine"],"prefix":"10.1002","volume":"21","author":[{"given":"Zhengyang","family":"Quan","sequence":"first","affiliation":[{"name":"School of Life Science Beijing Institute of Technology  Beijing 100081 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Science Beijing Institute of Technology  Beijing 100081 P. R. 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