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载有抗视网膜轴突导向分子1（RGMa）的人工小胶质细胞纳米平台用于急性缺血性卒中的再通和神经保护的声/磁场研究

Artificial Microglia Nanoplatform Loaded With Anti-RGMa in Acoustic/Magnetic Feld for Recanalization and Neuroprotection in Acute Ischemic Stroke.

作者信息

Cheng Ruiqi, Luo Xiaoqin, Wu Xiaohui, Wang Zijie, Chen Ziqun, Zhang Shaoru, Xiao Hongmei, Zhong Jiaju, Zhang Rongrong, Cao Yang, Qin Xinyue

机构信息

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, Ultrasound Department of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.

出版信息

Adv Sci (Weinh). 2024 Dec;11(48):e2410529. doi: 10.1002/advs.202410529. Epub 2024 Oct 30.

DOI:10.1002/advs.202410529
PMID:39475454
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11672321/
Abstract

Ischemic stroke is a leading cause of death and disability worldwide, and the main goals of stroke treatment are to destroy the thrombus to recanalize blood vessels and protect tissue from ischemia/reperfusion injury. However, current recanalization therapies have serious limitations and there are few neuroprotection methods. Hence, an artificial nanoplatform loaded with anti-Repulsive Guidance Molecule a monoclonal antibody (anti-RGMa) and coated with microglia membrane (MiCM) is reported for stroke treatment, namely MiCM@PLGA/anti-RGMa/FeO@PFH (MiCM-NPs). Tail vein injection of MiCM-NPs targeted the ischemia-damaged endothelial cells because of the MiCM, then superparamagnetic iron oxide (FeO) and anti-RGMa are released after external low-intensity focused ultrasound (LIFU) exposure. The thrombus is destroyed by LIFU-induced "liquid-to-gas" phase transition and cavitation of perfluorohexane (PFH) as well as FeO movements induced by an external magnetic field. Anti-RGMa protected the ischemic region from ischemia/reperfusion injury. The nanoplatform enabled visualization of the thrombus by ultrasound/photoacoustic imaging when the clot is in an extracranial artery. Importantly, in vivo animal studies revealed good safety for MiCM-NPs treatment. In conclusion, this nanoplatform shows promise as an ischemic stroke treatment strategy combining targeted delivery, recanalization, and neuroprotection.

摘要

缺血性中风是全球范围内导致死亡和残疾的主要原因，中风治疗的主要目标是破坏血栓以使血管再通，并保护组织免受缺血/再灌注损伤。然而，目前的再通疗法存在严重局限性，神经保护方法也很少。因此，据报道一种载有抗排斥导向分子a单克隆抗体（抗RGMa）并涂有小胶质细胞膜（MiCM）的人工纳米平台用于中风治疗，即MiCM@PLGA/抗RGMa/FeO@PFH（MiCM-NPs）。由于MiCM的存在，尾静脉注射MiCM-NPs可靶向缺血损伤的内皮细胞，然后在外部低强度聚焦超声（LIFU）照射后释放超顺磁性氧化铁（FeO）和抗RGMa。血栓通过LIFU诱导的全氟己烷（PFH）的“液-气”相变和空化以及外部磁场诱导的FeO运动而被破坏。抗RGMa保护缺血区域免受缺血/再灌注损伤。当血栓位于颅外动脉时，该纳米平台能够通过超声/光声成像实现血栓可视化。重要的是，体内动物研究表明MiCM-NPs治疗具有良好的安全性。总之，这种纳米平台作为一种结合靶向递送、再通和神经保护的缺血性中风治疗策略显示出前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5a1/11672321/ec55d358465d/ADVS-11-2410529-g008.jpg
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