Targeted-delivery of nanomedicine-enabled methylprednisolone to injured spinal cord promotes neuroprotection and functional recovery after acute spinal cord injury in rats

IF 4.2 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2024-06-11 DOI:10.1016/j.nano.2024.102761

Wei Zhao PhD , Zhenshan Jia PhD , William A. Bauman MD , Yiwen Qin BA , Yuanzhen Peng BA , Zihao Chen MS , Christopher P. Cardozo MD , Dong Wang PhD , Weiping Qin MD, Ph.D

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Abstract

To date, no therapy has been proven to be efficacious in fully restoring neurological functions after spinal cord injury (SCI). Systemic high-dose methylprednisolone (MP) improves neurological recovery after acute SCI in both animal and human. MP therapy remains controversial due to its modest effect on functional recovery and significant adverse effects. To overcome the limitation of MP therapy, we have developed a N-(2-hydroxypropyl) methacrylamide copolymer-based MP prodrug nanomedicine (Nano-MP) that can selectively deliver MP to the SCI lesion when administered systemically in a rat model of acute SCI. Our in vivo data reveal that Nano-MP is significantly more effective than free MP in attenuating secondary injuries and neuronal apoptosis. Nano-MP is superior to free MP in improving functional recovery after acute SCI in rats. These data support Nano-MP as a promising neurotherapeutic candidate, which may provide potent neuroprotection and accelerate functional recovery with improved safety for patients with acute SCI.

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在大鼠急性脊髓损伤后，向损伤脊髓靶向投放纳米药物甲基强的松龙可促进神经保护和功能恢复。

迄今为止，还没有一种疗法能有效地完全恢复脊髓损伤（SCI）后的神经功能。全身大剂量甲基强的松龙（MP）可改善动物和人类急性脊髓损伤后的神经功能恢复。由于甲基强的松龙疗法对功能恢复的作用不大，且有明显的不良反应，因此仍存在争议。为了克服MP疗法的局限性，我们开发了一种基于N-（2-羟基丙基）甲基丙烯酰胺共聚物的MP原药纳米药物（Nano-MP），在急性SCI大鼠模型中全身给药时可选择性地将MP递送至SCI病灶。我们的体内数据显示，纳米 MP 在减轻继发性损伤和神经细胞凋亡方面的效果明显优于游离 MP。在改善大鼠急性 SCI 后的功能恢复方面，纳米 MP 优于游离 MP。这些数据支持纳米MP成为一种很有前景的神经治疗候选药物，它可以为急性损伤患者提供有效的神经保护并加速功能恢复，同时提高安全性。

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来源期刊

Nanomedicine : nanotechnology, biology, and medicine 工程技术-纳米科技

CiteScore

11.10

自引率

0.00%

发文量

133

审稿时长

42 days

期刊介绍： The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.