Plasma–Nanomedicine Synergistic Therapy for Brain Diseases: Current Status, Applications, and Challenges

Brain diseases such as ischaemic stroke, Alzheimer's disease (AD), and glioma were characterized by high mortality and disability rate, and oxidative stress remains a major obstacle in treatment. Plasma-nanomedicine synergistic treatment technology provides a very attractive treatment strategy based on complementarity. This technology integrates cold atmospheric plasma (CAP) with nanomedicine. CAP produces active substances that regulate oxidative stress, while nanomedicine is specially designed for targeted delivery, controlled release, and microenvironmentally responsive activation of therapeutic agents. This integration generates new therapeutic functions and significantly improves the overall therapeutic effect. Despite the broad prospects of this emerging technology, researchers in the fields of medicine, physics, or pharmacy have not yet paid much attention to it. To fill this research gap, this review describes the physicochemical properties and biological effects of CAP and summarizes the latest advances in plasma nanomedicine strategies in the field of brain disease intervention, and reviews the four major nanomedical categories-metal-based, inorganic non-metallic, polymer-based and hydrogel systems-and their clinical applications in the treatment of brain tumors, strokes and neurodegenerative diseases in conjunction with CAP. Finally, we highlight a number of key challenges-limited resources of special CAP equipment, incomplete understanding of the mechanism, obstacles to transformation application-and put forward the future research direction to promote the development of accurate, safe, and clinical transformation value plasma-nanomedicine therapy for brain diseases.