文献：pH-Responsive Hexa-Histidine Metal Assembly (HmA) with Enhanced Biocatalytic Cascades as the Vehicle for Glucose-Mediated Long-Acting Insulin Delivery

文献链接：https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202301771

作者：Sijie Zhou , Ruhui Yang , Xiaoling Xie , Liwen Wang , Shengwu Zheng , Na Li , Sicheng Tang , Xingjie Zan

相关产品：FITC-insulin（FITC-胰岛素）

原文摘要：

Diabetes has been listed as one of the three major diseases that endanger human health. Accurately injecting insulin (Ins) depending on the level of blood glucose (LBG) is the standard treatment, especially controlling LBG in the long-term by a single injection. Herein, the pH-responsive hexa-histidine metal assembly (HmA) encapsulated with enzymes (GOx and CAT) and Ins (HmA@GCI) is engineered as the vehicle for glucose-mediated insulin delivery. HmA not only shows high proteins loading efficiency, but also well retained proteins activity and protect proteins from protease damage. Within HmA, the biocatalytic activities of enzymes and the efficiency of the cascade reaction between GOx and CAT are enhanced, leading to a super response to the change of LBG with insulin release and efficient clearance of harmful byproducts of GOx (H2O2). In the treatment of diabetic mice, HmA@GCI reduces LBG to normal in half an hour and maintains for more than 5 days by a single subcutaneous injection, and nearly 24 days with four consecutive injections. During the test period, no symptoms of hypoglycemia and toxicity to tissues and organs are observed. These results indicate that HmA@GCI is a safe and long-acting hypoglycemic agent with prospective clinical application.   

FITC - insulin 是异硫氰酸荧光素（FITC）标记的胰岛素。胰岛素是一种由胰腺 β 细胞分泌的蛋白质激素，在调节血糖水平等生理过程中起着关键作用。FITC 是一种荧光染料，能够与胰岛素分子结合，使得胰岛素在特定波长的光激发下可以发出荧光。FITC 含有异硫氰酸基团（-NCS），它可以与胰岛素分子上的伯胺基发生反应，形成稳定的硫脲键。通过这种方式将荧光标记物连接到胰岛素分子上。基于FITC - insulin 的性能，pH 响应型金属组装体 HmA@GCI的合成如下：

图：合成及机制示意

在超声条件下，将Zn(NO3)2·6H2O水溶液滴入含有His6 、GOx 、CAT 和Ins的溶液中。然后，溶液变成浅蓝色，进一步超声。随后，收集HmA@GCI纳米颗粒，离心，用去离子水洗涤。通过添加相应的蛋白质，按照相同的方法合成HmA@Ins、HmA@GI和HmA@GC纳米颗粒。

图：表征

结论：

该文献成功制备出基于FITC - insulin 合成的pH 响应型金属组装体 HmA@GCI。HmA不仅表现出较高的蛋白质装载效率，而且能很好地保留蛋白质活性并保护蛋白质免受蛋白酶损伤。实验结果表明HmA@GCI是一种安全、长效的降糖化合物，具有良好的应用前景。