Magnetic Targeting Nanocarriers Combined with Focusing Ultrasound for Enhanced Intracerebral Hemorrhage Therapy

Abstract Intracerebral hemorrhage (ICH) remains a significant cause of morbidity and mortality around the world, and surgery is still the most direct and effective way to remove ICH. However, the potential risks brought by surgery, such as normal brain tissue damage, post‐operative infection, and difficulty in removing deep hematoma, are still the main problems in the surgical treatment of ICH. Activation of the peroxisome proliferator‐activated receptor gamma (PPARγ) is reported to show a good therapeutic effect in hematoma clearance. Herein, a magnetic targeting nanocarrier loaded with a PPARγ agonist (15d‐PGJ2‐MNPs) is synthesized, which could be magnetically targeted and enriched in the area of the hematoma after intravenous injection. Subsequent application of focusing ultrasound (FUS) could enhance drug diffusion, which activates the PPARγ receptors on macrophages around the hematoma for better hematoma clearance. The 15d‐PGJ2‐MNP treatment alleviates brain injury, accelerates hematoma clearance, attenuates neuroinflammation, reduces brain edema and significantly improves the deficits in sensory and motor function and spatial learning ability in the ICH mouse model. This work proposes an effective magnetic targeting plus FUS method to treat ICH, highlighting its great potential in the treatment of hemorrhagic stroke.