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去铁胺的聚乙二醇化修饰对改善大鼠实验性脑卒中模型中的稳定性、细胞毒性和铁过载的作用

PEGylation of Deferoxamine for Improving the Stability, Cytotoxicity, and Iron-Overload in an Experimental Stroke Model in Rats.

作者信息

Xu Jiake, Sun Tong, Zhong Rui, You Chao, Tian Meng

机构信息

Neurosurgery Research Laboratory, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Front Bioeng Biotechnol. 2020 Sep 25;8:592294. doi: 10.3389/fbioe.2020.592294. eCollection 2020.

DOI:10.3389/fbioe.2020.592294
PMID:33102469
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7546414/
Abstract

Deferoxamine (DFO) is a widely used drug for the treatment of iron-overload-related diseases in the clinic. However, its inherent shortcomings, such as a short plasma half-life and cytotoxicity, need to be addressed to widen its clinical utility. In this study, PEGylated DFO was first synthesized, and its chemical structure was characterized, and then and studies were performed. The metabolism assay showed that the stability of the PEGylated DFO was significantly improved, with a half-life 20 times greater than DFO. Furthermore, the PEGylated DFO exhibited significantly lower cytotoxicity compared with DFO. Additionally, the hemocompatibility assay showed that the PEGylated DFO had no significant effect on the coagulation system, red blood cells, complement, and platelets. studies indicated that PEGylated DFO was capable of reducing the iron accumulation, degeneration of neurons, and promotion of functional recovery. Taken together, PEGylated DFO improved stability, cytotoxicity, and iron-overload in an experimental stroke model in rats, making it a promising therapy for treating iron-overload conditions in the clinic.

摘要

去铁胺（DFO）是临床上广泛用于治疗铁过载相关疾病的药物。然而，其固有的缺点，如血浆半衰期短和细胞毒性，需要解决以扩大其临床应用。在本研究中，首先合成了聚乙二醇化去铁胺（PEGylated DFO），并对其化学结构进行了表征，然后进行了[此处原文缺失相关内容]研究。代谢试验表明，聚乙二醇化去铁胺的稳定性显著提高，半衰期比去铁胺长20倍。此外，与去铁胺相比，聚乙二醇化去铁胺的细胞毒性显著降低。另外，血液相容性试验表明，聚乙二醇化去铁胺对凝血系统、红细胞、补体和血小板没有显著影响。[此处原文缺失相关内容]研究表明，聚乙二醇化去铁胺能够减少铁蓄积、神经元变性并促进功能恢复。综上所述，聚乙二醇化去铁胺改善了大鼠实验性中风模型中的稳定性、细胞毒性和铁过载，使其成为临床上治疗铁过载病症的一种有前景的疗法。

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