Nitric oxide (NO) is an essential signaling molecule with a number of biological functions and holds great promise in biomedical applications. However, NO delivery technologies have been complicated due to the inherent properties of NO which include short half-life and limited transport distance in human tissues. In addition, the biofunctionality of NO is strongly dependent on its concentrations and locations where it is delivered. To achieve controlled NO delivery, many studies have focused on encapsulating NO donors into macromolecular scaffolds or using catalysts to realize in situ NO generation from NO prodrugs. Successful applications have been shown, however NO donor-loaded platforms experience the limitation of finite NO storage capacity. The present study reports the synthesis of a catalyst, copper-doped zeolitic imidazolate framework ZIF-8 (Cu²⁺/ZIF-8), that is designed to generate NO from naturally occurring endogenous NO donors. By tuning the copper doping percentages, we achieved controlled NO generation from S-nitrosoglutathione (GSNO) and S-nitrosocysteine (CysNO). Cu²⁺/ZIF-8 particles retained their catalytic potency after 5 NO generation cycles and we showed that our copper-doped ZIF-8 catalyst produced a 10-fold increased amount of NO compared with previous reports. As a proof-of-concept study, we demonstrated the ability of copper-doped ZIF-8 to disperse bacterial biofilms in the presence of GSNO.

中文翻译：

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铜掺杂的金属有机框架，可控制内源性S-亚硝基硫醇生成一氧化氮

一氧化氮（NO）是具有多种生物学功能的重要信号分子，在生物医学应用中具有广阔的前景。但是，由于NO的固有特性（包括半衰期短和在人体组织中的运输距离有限），NO输送技术已经变得复杂。另外，NO的生物功能性在很大程度上取决于其浓度和其递送位置。为了实现受控的NO输送，许多研究都集中在将NO供体封装到大分子支架中或使用催化剂来原位实现。没有前药就不会产生。已经显示出成功的应用，但是，没有供体装载的平台受到有限的NO存储容量的限制。本研究报告了一种催化剂，即掺杂铜的沸石咪唑酸盐骨架ZIF-8（Cu ²⁺ / ZIF-8）的合成，该骨架旨在从天然存在的内源NO供体生成NO。通过调整铜的掺杂百分比，我们实现了由S-亚硝基谷胱甘肽（GSNO）和S-亚硝基半胱氨酸（CysNO）产生的受控NO生成。铜²⁺/ ZIF-8颗粒在5个NO生成循环后仍保持其催化效能，并且我们证明了与以前的报道相比，我们的铜掺杂ZIF-8催化剂产生的NO含量增加了10倍。作为概念验证研究，我们证明了铜掺杂ZIF-8在GSNO存在下分散细菌生物膜的能力。