In the past decades, insulin delivery systems have been widely developed for diabetes treatment. Though a few works have investigated polymeric micelles with glucose and H₂O₂ dual-responsiveness for the delivery of insulin, great efforts should still be devoted to enhancing the therapeutic efficacy. Herein, glucose/H₂O₂ dual-responsive polymeric micelles were fabricated for the self-regulated insulin delivery. The polymeric micelles were self-assembled by poly(ethylene glycol)-block-poly(amino phenylboronic ester) (PEG-b-PAPBE), where the hydrophilic PEG offered the shell and the hydrophobic PAPBE endowed the polymeric micelles with the dual-sensibility to glucose and H₂O₂. The built-in phenylboronic ester (PBE) could be not only broken by glucose but also hydrolyzed by H₂O₂, thus resulting in the disintegration of the polymeric micelles. The glucose-responsive release of insulin was achieved and could be further facilitated by the coencapsulation of glucose oxidase (GOx) in the micelles, which would produce H₂O₂ by catalytic oxidation of glucose and thus lead to the hydrolysis of the phenylboronic ester by H₂O₂. Compared with free insulin or micelles that carried insulin alone, a subcutaneous injection of the insulin/GOx-coloaded polymeric micelles to the diabetic mice presented a superior hypoglycemic effect in vivo. This kind of polymeric micelle with glucose and H₂O₂ dual-responsiveness provides a promising approach for diabetes therapy.

中文翻译：

---

葡萄糖和H ₂ O ₂双响应聚合物胶束用于胰岛素的自我调节释放

在过去的几十年中，已经广泛开发了用于糖尿病治疗的胰岛素递送系统。尽管一些工作已经研究了具有葡萄糖和H ₂ O ₂双重反应性的高分子胶束对胰岛素的递送，但仍应致力于提高治疗效果。在此，制造葡萄糖/ H ₂ O ₂双响应聚合物胶束用于自我调节的胰岛素递送。聚合物胶束自组装由聚（乙二醇） -嵌段-聚（氨基苯基酯）（PEG- b -PAPBE），其中，所述亲水性PEG提供的壳和疏水PAPBE赋有双敏感性的聚合物胶束葡萄糖和H₂ O ₂。内置的苯基硼酸酯（PBE）不仅会被葡萄糖破坏，还会被H ₂ O ₂水解，从而导致高分子胶束的分解。胰岛素对葡萄糖的响应释放得以实现，并且可以通过胶束中葡萄糖氧化酶（GOx）的共包封进一步促进，这将通过葡萄糖的催化氧化产生H ₂ O ₂，从而导致苯硼酸酯的水解。 H ₂ O ₂。与游离胰岛素或单独携带胰岛素的胶束相比，向糖尿病小鼠皮下注射胰岛素/ GOx负载的聚合胶束在体内具有更好的降血糖作用。这种具有葡萄糖和H ₂ O ₂双重反应性的聚合胶束为糖尿病治疗提供了一种有希望的方法。