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Glucose-Responsive Nanosystem Mimicking the Physiological Insulin Secretion via an Enzyme–Polymer Layer-by-Layer Coating Strategy
Chemistry of Materials ( IF 7.2 ) Pub Date : 2017-09-11 00:00:00 , DOI: 10.1021/acs.chemmater.7b01804 Chun Xu 1, 2 , Chang Lei 1 , Lili Huang 3 , Jun Zhang 1 , Hongwei Zhang 1 , Hao Song 1 , Meihua Yu 1 , Yeda Wu 3 , Chen Chen 3 , Chengzhong Yu 1
Chemistry of Materials ( IF 7.2 ) Pub Date : 2017-09-11 00:00:00 , DOI: 10.1021/acs.chemmater.7b01804 Chun Xu 1, 2 , Chang Lei 1 , Lili Huang 3 , Jun Zhang 1 , Hongwei Zhang 1 , Hao Song 1 , Meihua Yu 1 , Yeda Wu 3 , Chen Chen 3 , Chengzhong Yu 1
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Insulin administration mimicking physiological insulin secretion behavior remains a challenge for the treatment of patients with type I diabetes. Herein, we report a novel glucose-responsive insulin-release nanosystem through an enzyme–polymer layer-by-layer coating strategy on silica vesicles loaded with insulin. With a choice of polyethylenimine with prioritized proton binding capability and glucose specific enzymes in the coating layer, the insulin-release threshold can be adjusted in a desired glucose concentration range 5–20 mM for the first time. In vitro tests show that the insulin release is switched “ON” in response to hyperglycemia (10, 20 mM) and “OFF” to normal glucose level (5 mM) repeatedly. Moreover, in vivo experiments in type I diabetes mice demonstrate that our nanosystem enables a fast glucose response insulin release and regulates the glycemia levels in a normal range up to 84 h with a single administration. In addition, when applied to healthy mice, the nanosystem maintains the blood glucose concentration in the normal range without causing hypoglycemia. Our nanosystem which mimics the physiological insulin secretion has the potential to be developed as a convenient and safe insulin delivery carrier for diabetes treatment.
中文翻译：
葡萄糖-响应性纳米系统，通过酶-聚合物层涂层策略模拟胰岛素的生理分泌
模仿生理胰岛素分泌行为的胰岛素给药仍然是治疗I型糖尿病患者的挑战。在本文中，我们通过载有胰岛素的二氧化硅囊泡上的酶-聚合物逐层包衣策略报道了一种新型的葡萄糖反应性胰岛素释放纳米系统。通过选择具有优先质子结合能力和涂层中葡萄糖特异性酶的聚乙烯亚胺，可以首次将胰岛素释放阈值调节在所需的葡萄糖浓度范围5–20 mM中。体外试验表明，对高血糖症（10，20 mM）的响应是将胰岛素释放切换为“ ON”，而对正常血糖水平（5 mM）则反复将“ OFF”切换为“正常”。而且，体内在I型糖尿病小鼠中进行的实验表明，我们的纳米系统能够通过单次给药在84小时的正常范围内实现快速的葡萄糖响应胰岛素释放并调节血糖水平。另外，当应用于健康小鼠时，纳米系统将血糖浓度维持在正常范围内而不会引起低血糖症。我们的模仿生理胰岛素分泌的纳米系统有可能被开发为糖尿病治疗的便捷，安全的胰岛素输送载体。
更新日期：2017-09-11
中文翻译：
葡萄糖-响应性纳米系统，通过酶-聚合物层涂层策略模拟胰岛素的生理分泌
模仿生理胰岛素分泌行为的胰岛素给药仍然是治疗I型糖尿病患者的挑战。在本文中，我们通过载有胰岛素的二氧化硅囊泡上的酶-聚合物逐层包衣策略报道了一种新型的葡萄糖反应性胰岛素释放纳米系统。通过选择具有优先质子结合能力和涂层中葡萄糖特异性酶的聚乙烯亚胺，可以首次将胰岛素释放阈值调节在所需的葡萄糖浓度范围5–20 mM中。体外试验表明，对高血糖症（10，20 mM）的响应是将胰岛素释放切换为“ ON”，而对正常血糖水平（5 mM）则反复将“ OFF”切换为“正常”。而且，体内在I型糖尿病小鼠中进行的实验表明，我们的纳米系统能够通过单次给药在84小时的正常范围内实现快速的葡萄糖响应胰岛素释放并调节血糖水平。另外，当应用于健康小鼠时，纳米系统将血糖浓度维持在正常范围内而不会引起低血糖症。我们的模仿生理胰岛素分泌的纳米系统有可能被开发为糖尿病治疗的便捷，安全的胰岛素输送载体。
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