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血液相容性赖氨酸固定化甲壳素/碳纳米管微球的构建及其在血液净化治疗中的潜在应用

Construction of blood compatible lysine-immobilized chitin/carbon nanotube microspheres and potential applications for blood purified therapy.

作者信息

Wu Shuangquan, Duan Bo, Zeng Xianpeng, Lu Ang, Xu Xiaojuan, Wang Yanfeng, Ye Qifa, Zhang Lina

机构信息

College of Chemistry & Molecule Sciences, Wuhan University, Wuhan 430072, P. R. China.

出版信息

J Mater Chem B. 2017 Apr 28;5(16):2952-2963. doi: 10.1039/c7tb00101k. Epub 2017 Apr 5.

Abstract

Excess bilirubin often evokes hepatobiliary system dysfunction. In the present work, we developed an efficient, safe and blood compatible adsorbent for bilirubin removal from human blood. In view of the highly effective adsorption of carbon nanotubes (CNTs) on bilirubin but with many side effects, and good biocompatibility of chitin but with low efficiency for bilirubin removal, new chitin/carbon nanotube (Ch/CNT) nanofibrous microspheres were constructed from chitin solution in NaOH/urea aqueous system by blending with CNTs. The results of AFM, SEM, and TEM demonstrated that the CNTs were dispersed well in the chitin matrix, and the chitin nanofibers intertwined with CNTs to form hybrid chitin/CNT nanofibers and then weaved into a 3D interconnected network architecture. Moreover, lysine (Lys), a highly specific ligand for bilirubin, was immobilized tightly to the hybrid microspheres to obtain Ch/CNT/Lys. The resultant microspheres possessed large surface area and hierarchical pores including mesopores and micropores, which could allow bilirubin to enter easily and store, leading to highly efficient adsorption. The Ch/CNT/Lys microspheres exhibited excellent bilirubin adsorption property (107.2 mg g) and efficient bilirubin clearance rate from real hyperbilirubinemia plasma competing with protein, as well as good cell affinity and blood compatibility, as a result of the combination of the high adsorption of CNTs and inherent biocompatibility of chitin and lysine. Therefore, an effective strategy to develop a novel biocompatible and blood compatible bilirubin adsorbent is provided, showing potential applications for hemoperfusion in blood purified therapy.

摘要

过量胆红素常引发肝胆系统功能障碍。在本研究中,我们开发了一种高效、安全且与血液相容的吸附剂,用于从人血中去除胆红素。鉴于碳纳米管(CNTs)对胆红素具有高效吸附性但存在诸多副作用,而几丁质具有良好的生物相容性但去除胆红素效率较低,我们通过在NaOH/尿素水溶液体系中将几丁质溶液与CNTs混合,构建了新型几丁质/碳纳米管(Ch/CNT)纳米纤维微球。原子力显微镜(AFM)、扫描电子显微镜(SEM)和透射电子显微镜(TEM)结果表明,CNTs在几丁质基质中分散良好,几丁质纳米纤维与CNTs相互交织形成混合几丁质/CNT纳米纤维,进而编织成三维互连网络结构。此外,将胆红素的高特异性配体赖氨酸(Lys)紧密固定在混合微球上,得到Ch/CNT/Lys。所得微球具有大表面积和包括中孔和微孔在内的分级孔隙,这使得胆红素能够轻松进入并储存,从而实现高效吸附。由于CNTs的高吸附性与几丁质和赖氨酸固有的生物相容性相结合,Ch/CNT/Lys微球表现出优异的胆红素吸附性能(107.2 mg/g),在与蛋白质竞争的情况下,能从实际高胆红素血症血浆中高效清除胆红素,同时具有良好的细胞亲和力和血液相容性。因此,提供了一种开发新型生物相容性和血液相容性胆红素吸附剂的有效策略,显示出在血液净化治疗中血液灌流的潜在应用前景。

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