磁靶向纳米载体结合聚焦超声增强脑出血治疗,Small

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磁靶向纳米载体结合聚焦超声增强脑出血治疗
Small ( IF 13.0 ) Pub Date : 2023-01-26 , DOI: 10.1002/smll.202206982
Tianyi Wang ₁ , Huali Lei ₂ , Xiang Li ₁ , Nailin Yang ₂ , Cheng Ma ₁ , Guangqiang Li ₂ , Xiang Gao ₂ , Jun Ge ₂ , Zhuang Liu ₂ , Liang Cheng ₂ , Gang Chen ₁

Affiliation

脑出血 (ICH) 仍然是全世界发病率和死亡率的重要原因，手术仍然是去除 ICH 最直接、最有效的方法。然而，手术带来的潜在风险，如正常脑组织损伤、术后感染、深部血肿清除困难等，仍然是脑出血手术治疗的主要问题。据报道，过氧化物酶体增殖物激活受体 γ (PPARγ) 的激活在血肿清除中显示出良好的治疗效果。在此，合成了一种负载有 PPARγ 激动剂（15d-PGJ2-MNPs）的磁性靶向纳米载体，静脉注射后可在血肿区域进行磁性靶向和富集。随后应用聚焦超声 (FUS) 可以增强药物扩散，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，减少脑水肿，并显着改善 ICH 小鼠模型的感觉和运动功能以及空间学习能力的缺陷。这项工作提出了一种有效的磁靶向加 FUS 方法来治疗脑出血，突出了其在治疗出血性中风方面的巨大潜力。

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

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.

更新日期：2023-01-26

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