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抗P0抗体偶联纳米级造影剂靶向髓鞘用于术中可视化描绘颅神经

Anti-P0 Antibody-Conjugated Nanoscale Contrast Agent Targeting the Myelin Sheath for Intraoperative Visible Delineation of Cranial Nerves.

作者信息

Li Xiang, Zhang Si, Song Yuan-Qing, Tan Hong, Hui Xu-Hui

机构信息

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.

College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, People's Republic of China.

出版信息

ACS Biomater Sci Eng. 2020 Mar 9;6(3):1744-1754. doi: 10.1021/acsbiomaterials.9b01444. Epub 2020 Feb 10.

Abstract

The preservation of cranial nerves is a major problem that surgeons encounter when resecting a tumor in the posterior cranial fossa. Most cranial nerve injuries occur because the tight adhesion between the tumor capsule and cranial nerves renders the nerves indistinguishable. In this study, a nerve-specific nanoscale contrast agent was developed for visually distinguishing cranial nerves from the tumor surface in real time. To enable the contrast agent to specifically bind peripheral nerves, a previously reported biodegradable multiblock polyurethane nanoparticle (BMPU NP) was conjugated with an antibody against myelin protein zero (MPZ, P0), which is expressed on myelin sheaths in peripheral nerve fibers. Coomassie brilliant blue G (CB) was encapsulated into the BMPU NP for visual contrast. The CB-BMPU NP specifically stained mouse peripheral nerve fibers blue when directly applied to the nerve surface ex vivo and in vivo. The CB-BMPU NP also achieved satisfactory visual contrast of the trigeminal nerve in a mouse nerve-tissue adhesion model. This study offers new insights for the development of intraoperatively applied nerve-specific contrast agents for delineating cranial nerves adhered to tumors.

摘要

保留颅神经是外科医生在切除后颅窝肿瘤时遇到的一个主要问题。大多数颅神经损伤的发生是因为肿瘤包膜与颅神经之间的紧密粘连使得神经难以区分。在本研究中,开发了一种神经特异性纳米级造影剂,用于在肿瘤表面实时视觉区分颅神经。为了使造影剂能够特异性结合周围神经,将先前报道的可生物降解多嵌段聚氨酯纳米颗粒(BMPU NP)与抗髓磷脂蛋白零(MPZ,P0)抗体偶联,MPZ在周围神经纤维的髓鞘上表达。将考马斯亮蓝G(CB)封装到BMPU NP中以进行视觉对比。当在体外和体内直接应用于神经表面时,CB-BMPU NP将小鼠周围神经纤维特异性染成蓝色。在小鼠神经组织粘连模型中,CB-BMPU NP对三叉神经也实现了令人满意的视觉对比。本研究为开发术中应用的神经特异性造影剂以描绘与肿瘤粘连的颅神经提供了新的见解。

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