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荧光标记的抗神经节苷脂抗体可在活体动物中选择性识别外周神经。

Fluorescently-tagged anti-ganglioside antibody selectively identifies peripheral nerve in living animals.

作者信息

Massaad Cynthia A, Zhang Gang, Pillai Laila, Azhdarinia Ali, Liu Weiqiang, Sheikh Kazim A

机构信息

Department of Neurology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

Institute of Molecular Medicine-Center for Molecular Imaging, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

出版信息

Sci Rep. 2015 Oct 30;5:15766. doi: 10.1038/srep15766.

Abstract

Selective in vivo delivery of cargo to peripheral nervous system (PNS) has broad clinical and preclinical applications. An important applicability of this approach is systemic delivery of fluorescently conjugated ligands that selectively label PNS, which could allow visualization of peripheral nerves during any surgery. We examine the use of an anti-ganglioside monoclonal antibody (mAb) as selective neuronal delivery vector for surgical imaging of peripheral nerves. Systemic delivery of an anti-ganglioside mAb was used for selective intraneuronal/axonal delivery of fluorescent agents to visualize nerves by surgical imaging in living mice. In this study, we show that intact motor, sensory, and autonomic nerve fibers/paths are distinctly labeled following a single nanomolar systemic injection of fluorescently labeled anti-ganglioside mAb. Tissue biodistribution studies with radiolabeled mAb were used to validate neuronal uptake of fluorescently labeled mAb. Implications of this proof of concept study are that fluorescent conjugates of anti-ganglioside mAbs are valuable delivery vectors to visualize nerves during surgery to avoid nerve injury and monitor nerve degeneration and regeneration after injury. These findings support that antibodies, and their derivatives/fragments, can be used as selective neuronal delivery vector for transport of various cargos to PNS in preclinical and clinical settings.

摘要

将货物选择性地体内递送至外周神经系统(PNS)具有广泛的临床和临床前应用。这种方法的一个重要应用是全身递送荧光共轭配体,其可选择性标记PNS,这能够在任何手术过程中实现外周神经的可视化。我们研究了使用抗神经节苷脂单克隆抗体(mAb)作为外周神经手术成像的选择性神经元递送载体。抗神经节苷脂mAb的全身递送用于将荧光剂选择性地神经元内/轴突内递送,以通过活体小鼠的手术成像来可视化神经。在本研究中,我们表明,在单次纳摩尔全身注射荧光标记的抗神经节苷脂mAb后,完整的运动、感觉和自主神经纤维/路径被清晰地标记。使用放射性标记mAb的组织生物分布研究来验证荧光标记mAb的神经元摄取。这一概念验证研究的意义在于,抗神经节苷脂mAb的荧光共轭物是在手术期间可视化神经以避免神经损伤以及监测损伤后神经变性和再生的有价值的递送载体。这些发现支持抗体及其衍生物/片段可作为选择性神经元递送载体,用于在临床前和临床环境中将各种货物运输至PNS。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bd4/4626805/9ced0f74fbc6/srep15766-f1.jpg

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