Nitric Oxide Generation from Endogenous Substrates Using Metal-Organic Frameworks: Inclusion within Poly(vinyl alcohol) Membranes To Investigate Reactivity and Therapeutic Potential.
Nitric Oxide Generation from Endogenous Substrates Using Metal-Organic Frameworks: Inclusion within Poly(vinyl alcohol) Membranes To Investigate Reactivity and Therapeutic Potential.
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DOI：
10.1021/acsami.7b11846
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发表时间：
2017-10-18
影响因子：
9.5
通讯作者：
Reynolds MM
中科院分区：
文献类型：
--
作者：
Neufeld MJ;Lutzke A;Jones WM;Reynolds MM
Cu-BTTri (H3BTTri = 1,3,5-tris[1H 1,2,3-三唑-5-基]苯) 是一种水稳定的铜基金属有机框架 (MOF)，能够从血液中的 S-亚硝基硫醇 (RSNO) 生成治疗性一氧化氮 (NO)。将 Cu-BTTri 固定在聚合物膜内可能会在血液-材料界面处产生局部 NO。这项工作表明，Cu-BTTri 可以掺入由聚乙烯醇 (PVA) 制备的亲水膜中，聚乙烯醇是一种已被检验用于多种生物医学应用的聚合物。固定后，MOF 从内源 RSNO S-亚硝基谷胱甘肽 (GSNO) 产生 NO 的能力不会受到显着抑制。测试了含有 Cu-BTTri 分散体的聚乙烯醇膜在 pH 7.4 和 37 °C 下促进从 10 μM 初始 GSNO 浓度释放 NO 的能力，观察到 NO 产生水平与抗血栓治疗效果相关，且没有明显的铜浸出（<1%）。在 3.5 ± 0.4 小时内，10 wt% Cu-BTTri/PVA 膜将 97 ± 6% 的 GSNO 转化为 NO，最大 NO 通量为 0.20 ± 0.02 nmol·cm−2·min−1。此外，首次观察到 Cu-BTTri 能够在有氧条件下诱导 GSNO 产生 NO。在 pH 6.0 时，10 wt% Cu-BTTri/PVA 膜的 NO 形成反应加速了 22%，而在氯化铜 (II) 水溶液的情况下观察到相反的效果。降低温度 (20 °C) 和硫醇封闭剂 N-乙基马来酰亚胺 (NEM) 的存在会损害 Cu-BTTri/PVA 与 GSNO 的 NO 形成反应，这两种条件都会导致 3.5 小时内 NO 产量降低 16 ± 1%。总的来说，这些发现表明 Cu-BTTri/PVA 膜可能通过其从内源性底物产生 NO 的能力而具有治疗用途。此外，这项工作对影响 Cu-BTTri 功效的参数进行了更全面的分析，从而可以优化潜在的医疗应用。
Cu-BTTri (H3BTTri = 1,3,5-tris[1H 1,2,3-triazol-5-yl]benzene) is a water-stable, copper-based metal− organic framework (MOF) that exhibits the ability to generate therapeutic nitric oxide (NO) from S-nitrosothiols (RSNOs) available within the bloodstream. Immobilization of Cu-BTTri within a polymeric membrane may allow for localized NO generation at the blood−material interface. This work demonstrates that Cu-BTTri can be incorporated within hydrophilic membranes prepared from poly(vinyl alcohol) (PVA), a polymer that has been examined for numerous biomedical applications. Following immobilization, the ability of the MOF to produce NO from the endogenous RSNO S-nitrosoglutathione (GSNO) is not significantly inhibited. Poly(vinyl alcohol) membranes containing dispersions of Cu-BTTri were tested for their ability to promote NO release from a 10 μM initial GSNO concentration at pH 7.4 and 37 °C, and NO production was observed at levels associated with antithrombotic therapeutic effects without significant copper leaching (<1%). Over 3.5 ± 0.4 h, 10 wt % Cu-BTTri/PVA membranes converted 97 ± 6% of GSNO into NO, with a maximum NO flux of 0.20 ± 0.02 nmol·cm−2·min−1. Furthermore, it was observed for the first time that Cu-BTTri is capable of inducing NO production from GSNO under aerobic conditions. At pH 6.0, the NO-forming reaction of 10 wt % Cu-BTTri/PVA membrane was accelerated by 22%, while an opposite effect was observed in the case of aqueous copper(II) chloride. Reduced temperature (20 °C) and the presence of the thiol-blocking reagent N-ethylmaleimide (NEM) impair the NO-forming reaction of Cu-BTTri/PVA with GSNO, with both conditions resulting in a decreased NO yield of 16 ± 1% over 3.5 h. Collectively, these findings suggest that Cu-BTTri/PVA membranes may have therapeutic utility through their ability to generate NO from endogenous substrates. Moreover, this work provides a more comprehensive analysis of the parameters that influence Cu-BTTri efficacy, permitting optimization for potential medical applications.
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影响因子：
19
作者：
Harding, Jacqueline L.;Metz, Jarid M.;Reynolds, Melissa M.
通讯作者：
Reynolds, Melissa M.
DOI：
10.1039/p29960000481
发表时间：
1996-04-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2
影响因子：
--
作者：
Dicks, AP;Swift, HR;Cox, BG
通讯作者：
Cox, BG
影响因子：
3
作者：
Figueiredo, Katia C. S.;Alves, Tito L. M.;Borges, Cristiano P.
通讯作者：
Borges, Cristiano P.
影响因子：
3.7
作者：
Dhakshinamoorthy, Amarajothi;Alvaro, Mercedes;Garcia, Hermenegildo
通讯作者：
Garcia, Hermenegildo
影响因子：
3.7
作者：
Duke, Audrey S.;Dolgopolova, Ekaterina A.;Shustova, Natalia B.
通讯作者：
Shustova, Natalia B.