Glucose and pH dual‐responsive insulin delivery carriers that have been validated in animal models, remain elusive and much desired. Herein, a new class of covalent organic frameworks (COFs)‐based insulin delivery nanocarriers is developed by encapsulating insulin (Ins) and glucose oxidase (GOx) into COFs (COF‐1 and COF‐5) via both Brønsted and Lewis type (N:→B) complexations. Subsequently, polyethylene glycolated fluorescein isothiocyanate (FITC‐PEG) is incorporated into the COFs via the exchange reactions between the disulfide in insulin chains and the thiol in FITC‐PEG to afford a robust nano‐assembly (FITC‐PEG‐COF@Ins‐GOx). In vitro, the nanocarriers rely on the boroxine‐linked COFs’ response to pH and glucose dual‐stimulation and rendered sustainable insulin delivery. In vivo, the polymer–COFs composite displays excellent long‐acting anti‐diabetic effects on type 1 diabetic mice within 72 h without side effects after one injection. More intriguingly, the nanocomposites also show great promise for the efficient delivery of native proteins with high generality. To the authors’ knowledge, this represents the first study pertaining to a facile methodology to prepare COF‐based insulin‐delivery nanocarriers for in vitro and in vivo therapeutic applications.

中文翻译：

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用于小鼠体内葡萄糖和pH双反应胰岛素的聚合物-共价有机骨架复合材料。

在动物模型中已验证的葡萄糖和pH双重反应胰岛素递送载体仍然难以捉摸，并且非常需要。在此，通过将胰岛素（Ins）和葡萄糖氧化酶（GOx）通过布朗斯台德（Brønsted）和路易斯型（Lewis type）（N）封装到COF（COF-1和COF-5）中，开发了一种基于共价有机框架（COFs）的新型胰岛素输送纳米载体。 ：→B）复杂化。随后，通过胰岛素链中的二硫键和FITC-PEG中的硫醇之间的交换反应，将聚乙二醇化异硫氰酸荧光素（FITC-PEG）掺入COF中，以提供坚固的纳米组件（FITC-PEG-COF @ Ins-GOx ）。在体外，纳米载体依赖于与环硼氧烷相关的COF对pH和葡萄糖双重刺激的反应，并实现可持续的胰岛素输送。体内，聚合物-COFs复合材料在72小时内对1型糖尿病小鼠表现出出色的长效抗糖尿病作用，一次注射后无副作用。更有趣的是，纳米复合材料还显示出以高通用性有效递送天然蛋白质的巨大希望。据作者所知，这是有关用于体外和体内治疗应用制备基于COF的胰岛素释放纳米载体的简便方法的第一项研究。