Department of Environmental Engineering, North China Institute of Science and Technology, P.O. Box 206, Yanjiao, Beijing 101601, P. R. China.
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, P. R. China.
Biomacromolecules. 2020 Apr 13;21(4):1507-1515. doi: 10.1021/acs.biomac.0c00067. Epub 2020 Mar 13.
An intelligent carrier system is based on fast glucose response mechanism to regulate the insulin release. Here, glucose dual-responsive nanoparticles were quickly and efficiently obtained, by dynamic covalent bonds between phenylboronic acid-containing homopolymer poly(3-acrylamidophenylboronic acid) (PAAPBA) and glycopolypeptide poly(ethylene glycol)--poly(aspartic acid--aspart-glucosamine) (PEG--P(Asp--AGA)) through the formation of cycloborates. Meanwhile, insulin and glucose oxidase (GOx) were loaded during the formation of nanoparticles. The cycloborates in the nanoparticles could be destroyed by the replacement of glycosyl moieties by glucose and oxidized by HO generated from the glucose-GOx system, resulting in the rapid insulin release. After subcutaneous delivery of the insulin/GOx-loaded nanoparticles to diabetic mice, a significant hypoglycemic effect was observed over time. Cytotoxicity study, hemolysis assay, and histological analyses suggested that the nanoparticles showed excellent biocompatibility and safety. This work lays the important theoretical and technical foundations for expanding the scope of applications of nanocarriers in diabetes treatment.
智能载体系统基于快速葡萄糖响应机制来调节胰岛素释放。在这里，通过含苯硼酸的均聚物聚（3-丙烯酰胺基苯硼酸）（PAAPBA）和糖肽聚乙二醇-聚（天冬氨酸-天冬酰胺-葡萄糖胺）（PEG-P（Asp-AGA））之间的动态共价键，快速有效地获得了葡萄糖双响应纳米粒子。同时，在纳米粒子的形成过程中负载了胰岛素和葡萄糖氧化酶（GOx）。纳米粒子中的环硼酸酯可以通过葡萄糖取代糖基部分被破坏，并被葡萄糖-GOx 系统产生的 HO 氧化，导致胰岛素的快速释放。将负载胰岛素/GOx 的纳米粒子经皮下递送至糖尿病小鼠后，随着时间的推移，观察到显著的降血糖作用。细胞毒性研究、溶血试验和组织学分析表明，纳米粒子表现出优异的生物相容性和安全性。这项工作为扩展纳米载体在糖尿病治疗中的应用范围奠定了重要的理论和技术基础。
