Accessing neuroinflammation sites: Monocyte/neutrophil-mediated drug delivery for cerebral ischemia

进入神经炎症部位:单核细胞/中性粒细胞介导的脑缺血药物输送

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作者:Jia Hou, Xu Yang, Shiyi Li, Zhekang Cheng, Yuhua Wang, Jing Zhao, Chun Zhang, Yongji Li, Man Luo, Hongwei Ren, Jianming Liang, Jue Wang, Jianxin Wang, Jing Qin

Abstract

Cerebral ischemia (CI) results from inadequate blood flow to the brain. The difficulty of delivering therapeutic molecules to lesions resulting from CI hinders the effective treatment of this disease. The inflammatory response following CI offers a unique opportunity for drug delivery to the ischemic brain and targeted cells because of the recruitment of leukocytes to the stroke core and penumbra. In the present study, neutrophils and monocytes were explored as cell carriers after selectively carrying cRGD liposomes, which effectively transmigrated the blood-brain barrier, infiltrated the cerebral parenchyma, and delivered therapeutic molecules to the injured sites and target cells. Our results showed the successful comigration of liposomes with neutrophils/monocytes and that both monocytes and neutrophils were important for successful delivery. Enhanced protection against ischemic injury was achieved in the CI/reperfusion model. The strategy presented here shows potential in the treatment of CI and other diseases related to inflammation.

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