用于光分解和吸附胆红素的紫外线激活 "蓝灯泡":去除与蛋白质结合的毒素的战略性纳米结构

IF 21.1 1区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY
Yilin Wang , Ran Wei , Xijing Yang , Jiahao Liang , Xianda Liu , Shengjun Cheng , Shifan Chen , Ziyue Ling , Yujie Xiao , Yuanting Xu , Weifeng Zhao , Changsheng Zhao
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引用次数: 0

摘要

在长期接受血液净化治疗的患者中,蛋白质的大量流失很常见,死亡风险与血清白蛋白浓度之间存在很强的反比关系。清除毒素并留下白蛋白是血液净化领域的一项艰巨任务。受蛋白结合毒素在肾小管中解离-转运过程的启发,我们提出了多点光分解伴随吸附策略,作为血液灌流中的一种新型治疗模式。胆红素是一种典型的蛋白结合毒素,需要通过与血液环境中的白蛋白强结合来运输,因此我们选择胆红素作为研究对象,以验证这一概念。有趣的是,蓝光可以有效地将胆红素分解成一些极性很强的水溶性重氮化合物,而胆红素的分解产物是水溶性的,与白蛋白结合松散。在这里,石墨烯量子点(GQDs)和高分子科学在纳米架构过程中得到了结合。通过将石墨烯量子点嵌入聚(二烯丙基二甲基氯化铵-丙烯酰胺)(聚(DDAC-AAm)水凝胶(PDMG)微球,设计了 "光分解-吸附 "平台。为了减少阳离子聚合物对血液成分的影响,PDMG(PDMG@HA)微球表面通过静电作用包覆了透明质酸(HA)。由于 GQDs 的发光特性,PDMG@HA 微球在紫外线激活下会发出蓝光,并将胆红素分解成水溶性重氮化合物,就像无数个 "蓝灯泡 "一样。水溶性胆红素碎片可与白蛋白分离,被 "蓝灯泡 "吸附,大大减轻了机体的代谢负担。体外生物相容性结果表明,与 PDMG 微球相比,PDMG@HA 微球的蛋白质吸附性和血细胞毒性更低。在体外,胆红素的光分解和吸附量为 187.8 毫克/克。在高胆红素血症家兔血液灌流中,"蓝球 "能清除血浆中 70.9% 的总胆红素(TBIL),延缓胆道梗阻对肝脏的损害。值得注意的是,胆红素光分解作用一直持续到治疗结束,部分胆红素残渣已被 "蓝球 "吸附。光分解与吸附相结合的策略为治疗血液相关疾病开辟了一条新途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

UV-activated “blue bulbs” for photodecomposition and adsorption of bilirubin: Strategic nanoarchitectonics to remove protein-bound toxins

UV-activated “blue bulbs” for photodecomposition and adsorption of bilirubin: Strategic nanoarchitectonics to remove protein-bound toxins
Massive loss of proteins is common in patients on long-term blood purification therapy, there is a strong inverse association between the risk of death and serum albumin concentration. Removing toxins and leaving behind albumin is an arduous task in the field of blood purification. Inspired by the dissociation-transportation process of protein-bound toxins in renal tubule, we propose multi-point photodecomposition accompany with adsorption strategy as a novel treatment modality in hemoperfusion. As a proof of concept, bilirubin is chosen as the research object since it is a typical protein-bound toxin that needs to be transported by strong binding to albumin in blood environment. Interestingly, blue light can efficiently break bilirubin into some highly polar water soluble diazo compounds, the decomposed products of bilirubin are water-soluble and loosely bound to albumin. Herein, graphene quantum dots (GQDs) and polymer science are combined in the nanoarchitectonics processes. The “photodecomposition-adsorption” platform is designed by embedding GQDs in poly (diallyldimethylammonium chloride-acrylamide) (poly (DDAC-AAm) hydrogel (PDMG) microspheres. In order to reduce the influence of cationic polymer on blood component, hyaluronic acid (HA) are coated on the surface of the PDMG (PDMG@HA) microspheres by electrostatic interaction. Owing to the luminescence property of GQDs, the PDMG@HA microspheres emit blue light under ultraviolet activation and decompose bilirubin into water soluble diazo compounds, just like numerous “blue bulbs”. The water-soluble bilirubin debris could be dissociated from albumin and adsorbed by “blue bulbs”, which greatly reduce the metabolic burden on the body. In vitro biocompatibility results demonstrate that the PDMG@HA microspheres show lower protein adsorption and blood cell toxicity than the PDMG microspheres. The photodecomposition and adsorption amount of bilirubin is 187.8 mg/g in vitro. In hyperbilirubinemia rabbit hemoperfusion, the “blue bulbs” remove 70.9 % total bilirubin (TBIL) from plasma and defer the liver damage of biliary obstruction. Notably, the bilirubin photodecomposition is persisted to the end of the treatment, and some of the bilirubin debris have been adsorbed by the “blue bulbs”. The strategy combining both photodecomposition and adsorption opens a new route for the treatment of blood-related diseases.
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来源期刊
Materials Today
Materials Today 工程技术-材料科学:综合
CiteScore
36.30
自引率
1.20%
发文量
237
审稿时长
23 days
期刊介绍: Materials Today is the leading journal in the Materials Today family, focusing on the latest and most impactful work in the materials science community. With a reputation for excellence in news and reviews, the journal has now expanded its coverage to include original research and aims to be at the forefront of the field. We welcome comprehensive articles, short communications, and review articles from established leaders in the rapidly evolving fields of materials science and related disciplines. We strive to provide authors with rigorous peer review, fast publication, and maximum exposure for their work. While we only accept the most significant manuscripts, our speedy evaluation process ensures that there are no unnecessary publication delays.
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