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基于金属有机骨架的氧载体,通过聚多巴胺涂层实现抗氧化保护。

Metal-organic framework-based oxygen carriers with antioxidant protection as a result of a polydopamine coating.

机构信息

DTU Health Tech, Centre for Nanomedicine and Theranostics, Technical University of Denmark, Nils Koppels Allé, B423, 2800 Kgs. Lyngby, Denmark.

EXPEC Advanced Research Center, Saudi Aramco, PO13889, Saudi Aramco, Dhahran, 31311, Saudi Arabia.

出版信息

Biomater Sci. 2021 Oct 26;9(21):7257-7274. doi: 10.1039/d1bm01005k.

Abstract

Rapid haemorrhage control to restore tissue oxygenation is essential in order to improve survival following traumatic injury. To this end, the current clinical standard relies on the timely administration of donor blood. However, limited availability and portability, special storage requirements, the need for blood type matching and risks of disease transmission result in severe logistical challenges, impeding the use of donor blood in pre-hospital scenarios. Therefore, great effort has been devoted to the development of haemoglobin (Hb)-based oxygen carriers (HBOCs), which could be used as a "bridge" to maintain tissue oxygenation until hospital admission. HBOCs hold the potential to diminish the deleterious effects of acute bleeding and associated mortality rates. We recently presented a novel HBOC, consisting of Hb-loaded metal organic framework (MOF)-based nanoparticles (NPs) (MOF-NPs), and demonstrated its ability to reversibly bind and release oxygen. However, a long standing challenge when developing HBOCs is that, over time, Hb oxidizes to non-functional methaemoglobin (metHb). Herein, we address this challenge by modifying the surface of the as-prepared MOF-NPs with an antioxidant polydopamine (PDA) coating. The conditions promoting the greatest PDA deposition are first optimized. Next, the ability of the resulting PDA-coated MOF-NPs to scavenge important reactive oxygen species is demonstrated both in a test tube and in the presence of two relevant cell lines (, macrophages and endothelial cells). Importantly, this antioxidant protection translates into minimal metHb conversion.

摘要

迅速止血以恢复组织氧合对于创伤后提高生存率至关重要。为此,目前的临床标准依赖于及时输注供体血液。然而,供体血液的可用性和便携性有限、特殊的储存要求、血型匹配的需要以及疾病传播的风险,导致在院前场景中使用供体血液存在严重的后勤挑战。因此,人们付出了巨大努力来开发血红蛋白(Hb)基氧载体(HBOC),它可以作为一种“桥梁”,在入院前维持组织氧合。HBOC 有可能减轻急性出血和相关死亡率的有害影响。我们最近提出了一种新型 HBOC,由负载 Hb 的金属有机骨架(MOF)基纳米颗粒(NPs)(MOF-NPs)组成,并证明了它可逆结合和释放氧气的能力。然而,开发 HBOC 的一个长期挑战是,随着时间的推移,Hb 会氧化为非功能性高铁血红蛋白(metHb)。在此,我们通过用抗氧化剂聚多巴胺(PDA)涂层修饰制备好的 MOF-NPs 的表面来解决这一挑战。首先优化了促进 PDA 沉积的最佳条件。接下来,证明了所得的 PDA 涂层 MOF-NPs 在试管中和两种相关细胞系(巨噬细胞和内皮细胞)中清除重要活性氧物种的能力。重要的是,这种抗氧化保护转化为最小的 metHb 转化率。

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