文献类型：期刊文献

英文题名：Poly(bis(guanidinium)-oxazoline)-Insulin Complex Exerting Long-Acting Glucose-Responsive Insulin Release in Mice and Minipigs

作者：Zhang, Haodong[1];Liang, Qian[2];Jiang, Weinan[3];Chen, Qi[2];Chen, Kang[2,3];Cong, Zihao[2,3];Liu, Guojian[2];Shi, Jia[2];Ji, Yanxiu[2];Li, Wenxin[2];Dou, Mengyue[2];Wang, Yuwen[2];Liu, Longqiang[2,3];Chen, Luhang[2];Zhang, Donghui[1];Wu, Yueming[2];Liu, Runhui[1,2,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Engn Res Ctr Biomed Mat,Minist Educ,Sch Mat Sci &, Key Lab Ultrafine Mat,Minist Educ,Frontiers Sci Ct, Shanghai 200237, Peoples R China;[3]Chinese Acad Sci, Suzhou Inst Biomed Engn & Technol, Suzhou 215163, Peoples R China

年份：2025

卷号：147

期号：44

起止页码：40576

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20254519451955);WOS:【SCI-EXPANDED(收录号:WOS:001599150000001)】；

基金：This research was supported by the National Natural Science Foundation of China (No. T2325010), the Chinese Academy of Sciences Project for Young Scientists in Basic Research (Grant No.YSBR-111), Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission), and the Fundamental Research Funds for the Central Universities (Nos. JKVD1241029 and JKD01241701). We also thank the Research Center of Analysis and Test of East China University of Science and Technology for help with the characterization. We also thank the staff members of the Integrated Laser Microscopy System at the National Facility for Protein Science in Shanghai (NFPS), Zhangjiang Laboratory, China, Shanghai Ruijin Rehabilitation Hospital, Hubei BIOSSCI Biotechnology Co., Ltd., and Shanghai Jiagan Biotechnology Co., Ltd. for providing technical support and assistance in data collection and analysis.

语种：英文

外文关键词：Electrostatics - Glucose - Insulin - Mammals

摘要：Glucose-responsive insulin formulations, utilizing electrostatic interactions between positively charged polymers and negatively charged insulin, offer significant potential to enhance the therapeutic index of insulin while alleviating the burden of frequent administration. However, their clinical application is limited by concerns on the uncontrolled insulin release, including the dangerous hypoglycemic events. Here, we develop a glucose-responsive insulin formulation for subcutaneous administration, which exhibits exceptional biocompatibility and maintains normoglycemia over 192 h in type 1 diabetic minipigs after a single dose, with negligible hypoglycemia. The formulation comprises recombinant human insulin, tightly binding to bis(guanidinium)-functionalized poly(2-oxazoline) polymers, which are further modified with phenylboronic acid to enable glucose responsive insulin release. Bis-guanidinium strengthens the electrostatic interaction with insulin, thereby preventing uncontrolled insulin release and prolonging the therapeutic effect in vivo. This bis(guanidinium)-functionalized polymer strategy opens new avenues for developing glucose-responsive insulin formulations.