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Interface Components: Nanoparticles, Colloids, Emulsions, Surfactants, Proteins, Polymers
Nitrilotriacetic Acid Functionalized Glucose-Responsive Complex Micelles for Efficient Encapsulation and Self-Regulated Release of Insulin Chang Li, Fan Huang, Yong Liu, Juan Lv, Gang Wu, Ying Liu, Rujiang Ma, Yingli An, and Linqi Shi Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.8b02574 • Publication Date (Web): 13 Sep 2018 Downloaded from http://pubs.acs.org on September 13, 2018
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Langmuir
Nitrilotriacetic Acid Functionalized Glucose-Responsive Complex Micelles for Efficient Encapsulation and Self-Regulated Release of Insulin Chang Li,ǁ,† Fan Huang,ǁ,§ Yong Liu,† Juan Lv,† Gang Wu,† Ying Liu,† Rujiang Ma,†,* Yingli An,† and Linqi Shi†,‡,* †
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional
Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China. §
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute
of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China. ‡
Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai
University, Tianjin 300071, China.
ABSTRACT: Insulin plays a significant role in diabetes treatment. Although a huge number of insulin-loaded, glucose-responsive nanocarriers have been developed in the past decades, most of them showed lower loading capacity and efficiency due to the weak interaction between insulin and nanocarriers. In this work, a novel insulin-encapsulated glucose-responsive polymeric complex micelles (CM) is devised, showing (i) enhanced insulin loading efficiency owing to the zinc ions chelation by nitrilotriacetic acid (NTA) groups of NTA-functioned glycopolymer and histidine imidazole of insulin, (ii) glucose-triggered pulse release of insulin, and (iii) long stability under physiological conditions. This CM was fabricated by the self-assembly of block copolymer PEG-b-P(Asp-co-AspPBA) and glycopolymer P(Asp-co-AspGA-co-AspNTA), resulting in complex micelles with PEG shell and a cross-linked core composed of phenylboronic acid (PBA)/glucose complexations. Notably, the modified nitrilotriacetic acid (NTA) 1 / 23
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groups of CM could specifically bind insulin via chelated zinc ions, thus enhance the loading efficacy of insulin, compared to the non-modified CM. The dynamic PBA/glucose complexation core of CM dissociate under the trigger of high glucose concentration (>2 g/L), while being quite stable in low glucose concentration (
