Wang Tianyi, Lei Huali, Li Xiang, Yang Nailin, Ma Cheng, Li Guangqiang, Gao Xiang, Ge Jun, Liu Zhuang, Cheng Liang, Chen Gang
Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China.
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China.
Small. 2023 Apr;19(17):e2206982. doi: 10.1002/smll.202206982. Epub 2023 Jan 26.
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.
脑出血(ICH)仍是全球发病和死亡的重要原因,手术仍然是清除脑出血最直接有效的方法。然而,手术带来的潜在风险,如正常脑组织损伤、术后感染以及深部血肿清除困难等,仍是脑出血外科治疗的主要问题。据报道,过氧化物酶体增殖物激活受体γ(PPARγ)的激活在血肿清除方面显示出良好的治疗效果。在此,合成了一种负载PPARγ激动剂的磁性靶向纳米载体(15d-PGJ2-MNPs),静脉注射后可被磁性靶向并富集在血肿部位。随后应用聚焦超声(FUS)可增强药物扩散,激活血肿周围巨噬细胞上的PPARγ受体,以更好地清除血肿。15d-PGJ2-MNP治疗可减轻脑损伤,加速血肿清除,减轻神经炎症,减轻脑水肿,并显著改善脑出血小鼠模型的感觉和运动功能缺陷以及空间学习能力。这项工作提出了一种有效的磁性靶向加FUS方法来治疗脑出血,凸显了其在出血性中风治疗中的巨大潜力。
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