A Tunable, Stable, and Bioactive MOF Catalyst for Generating a Localized Therapeutic from Endogenous Sources
A Tunable, Stable, and Bioactive MOF Catalyst for Generating a Localized Therapeutic from Endogenous Sources
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DOI：
10.1002/adfm.201402529
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发表时间：
2014-12-17
影响因子：
19
通讯作者：
Reynolds, Melissa M.
中科院分区：
文献类型：
--
作者：
Harding, Jacqueline L.;Metz, Jarid M.;Reynolds, Melissa M.
金属有机框架（MOFs）的多功能化学和物理性质使其成为设计仿生催化剂的独特平台，但由于在生理环境中使用的MOFs的不稳定性，迄今为止仅取得有限的成功。在此，使用Cu（II）1，3，5-苯-三唑（CuBTTri）被证明用于从内源性来源S-亚硝基硫醇（RSNO）催化生成生物活性剂一氧化氮（NO）。CuBTTri在水性环境中表现出结构完整性，包括磷酸盐缓冲盐水（76 h，pH 7.4，37 ℃）、用于体外测试的细胞培养基（76 h，pH 7.4，37 ℃）和新鲜柠檬酸盐全血（30 min，pH 7.4，37 ℃）。通过将CuBTTri混合到生物医学级聚氨酯基质中形成复合材料CuBTTripoly，探索了CuBTTri在聚合物医疗器械中的应用。一旦制备，CuBTTri-聚材料保留了对NO生成的催化功能，其具有与嵌入聚合物材料中的CuBTTri的总含量成比例的可调释放动力学，具有对应于1-100 nM cm（-2）min（-1）的治疗范围的表面通量，即使在暴露于血液后也保持该表面通量。
The versatile chemical and physical properties of metal organic frameworks (MOFs) have made them unique platforms for the design of biomimetic catalysts, but with only limited success to date due to instability of the MOFs employed in physiological environments. Herein, the use of Cu(II) 1,3,5-Benzene-tris-triazole (CuBTTri) is demonstrated for the catalytic generation of the bioactive agent nitric oxide (NO) from endogenous sources, S-nitrosothiols (RSNOs). CuBTTri exhibits structural integrity in aqueous environments, including phosphate buffered saline (76 h, pH 7.4, 37 degrees C), cell media used for in vitro testing (76 h, pH 7.4, 37 degrees C), and fresh citrated whole blood (30 min, pH 7.4, 37 degrees C). The application of CuBTTri for use in polymeric medical devices is explored through the formation of a composite CuBTTripoly by blending CuBTTri into biomedical grade polyurethane matrices. Once prepared, the CuBTTri-poly material retains the catalytic function towards the generation of NO with tunable release kinetics proportional to the total content of CuBTTri embedded into the polymeric material with a surface flux corresponding to the therapeutic range of 1-100 nM cm(-2) min(-1), which is maintained even following exposure to blood.