Protein drugs play a significant role in the treatment of many diseases such as diabetes, cancers, and immune system diseases. Though polymeric nanocarriers have been designed to deliver protein drugs for prolonging circulation lifetime and providing stimuli-triggered release, problems are still often encountered including lower loading efficiency and capacity as well as poor circulation stability because of the weak interaction between protein drugs and nanocarriers. Herein, we described a new kind of bifunctional polymeric nanogels for efficient loading and glucose-triggered release of insulin. Biodegradable poly(N-isopropylacrylamide) (PNIPAM)-based nanogels was synthesized with nitrilotriacetic acid (NTA) and phenylboronic acid (PBA) as functional groups and ethylene glycol dimethacrylate (EGDMA) as cross-linker. The NTA groups could specifically bind imidazole-containing protein drugs such as insulin via chelated zinc ions, leading an efficient loading of insulin. The structure, morphology, and drug-loading properties of the nanogels were well-characterized, and glucose-triggered insulin release was achieved based on the glucose-responsiveness of PBA groups. MTT assay and enzymatic degradation revealed good biocompatibility and biodegradability for the nanogels. This kind of bifunctional nanogels would be promising candidates for glucose-responsive delivery of insulin in the future.

中文翻译：

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硝基三乙酸（NTA）和苯硼酸（PBA）功能化的纳米凝胶，可有效地封装和控制胰岛素的释放

蛋白药物在许多疾病的治疗中起着重要作用，例如糖尿病，癌症和免疫系统疾病。尽管已经设计了聚合物纳米载体来递送蛋白药物以延长循环寿命并提供刺激触发的释放，但是由于蛋白药物与纳米载体之间的弱相互作用，仍然经常遇到问题，包括较低的负载效率和容量以及较差的循环稳定性。在本文中，我们描述了一种新型的双功能聚合物纳米凝胶，可有效负载胰岛素并通过葡萄糖触发释放。可生物降解的聚（N以次氮基三乙酸（NTA）和苯基硼酸（PBA）为官能团，以乙二醇二甲基丙烯酸酯（EGDMA）为交联剂，合成了基于-（异丙基丙烯酰胺）（PNIPAM）的纳米凝胶。NTA基团可以通过螯合的锌离子特异性结合含咪唑的蛋白质药物（例如胰岛素），从而有效地负载胰岛素。纳米凝胶的结构，形态和载药特性得到了很好的表征，并且基于PBA基团的葡萄糖反应性，实现了葡萄糖触发的胰岛素释放。MTT分析和酶促降解显示纳米凝胶具有良好的生物相容性和生物降解性。这种双功能纳米凝胶将在将来成为葡萄糖响应性胰岛素输送的有希望的候选者。