Magnetic Field Driven Ceria Nanosystems for Mitochondria Targeted Therapy of Ischemic Stroke

Abstract Nanomedicine based brain targeting strategies have emerged as a promising avenue for ischemic stroke (IS) treatment. However, conventional targeting approaches face significant challenges in manipulating biodistribution and achieving efficient brain targeting to attain adequate therapeutic effects. Here, this limitation is overcame by developing a magnetic field driven, mitochondria‐targeted ceria nanosystem (MMTCe) nanosystem. By anchoring magnetic nanoparticles to the cell membrane, efficient brain targeted delivery of the nanosystem is achieved through the use of an external magnetic field, which in turn targets damaged mitochondria and repairs the ischemic microenvironment. MMTCe exhibits superior accumulation in the brain within an in vitro blood brain barrier (BBB) model and in a rat model of stroke. This targeting mediates mitochondrial function, thereby inhibiting oxidative stress and aberrant activation of microglial cells, ultimately inducing rebalancing of the ischemic microenvironment. Complemented by a favorable biosafety profile, the top‐down fabrication of MMTCe provides a general targeting strategy for brain diseases and informs the development of magnetically driven brain targeted delivery systems.