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Polymer–Covalent Organic Frameworks Composites for Glucose and pH Dual‐Responsive Insulin Delivery in Mice
Author(s) -
Zhang Guiyang,
Ji Yan,
Li Xinle,
Wang Xiaoyun,
Song Mengmeng,
Gou Huilin,
Gao Shan,
Jia Xudong
Publication year - 2020
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.202000221
Subject(s) - nanocarriers , glucose oxidase , insulin , covalent bond , chemistry , in vivo , pegylation , drug delivery , insulin delivery , fluorescein isothiocyanate , materials science , combinatorial chemistry , nanotechnology , polyethylene glycol , biochemistry , organic chemistry , biosensor , fluorescence , diabetes mellitus , type 1 diabetes , medicine , microbiology and biotechnology , endocrinology , biology , physics , quantum mechanics
Glucose and pH dual‐responsive insulin delivery carriers that have been validated in animal models, remain elusive and much desired. Herein, a new class of covalent organic frameworks (COFs)‐based insulin delivery nanocarriers is developed by encapsulating insulin (Ins) and glucose oxidase (GOx) into COFs (COF‐1 and COF‐5) via both Brønsted and Lewis type (N:→B) complexations. Subsequently, polyethylene glycolated fluorescein isothiocyanate (FITC‐PEG) is incorporated into the COFs via the exchange reactions between the disulfide in insulin chains and the thiol in FITC‐PEG to afford a robust nano‐assembly (FITC‐PEG‐COF@Ins‐GOx). In vitro, the nanocarriers rely on the boroxine‐linked COFs’ response to pH and glucose dual‐stimulation and rendered sustainable insulin delivery. In vivo, the polymer–COFs composite displays excellent long‐acting anti‐diabetic effects on type 1 diabetic mice within 72 h without side effects after one injection. More intriguingly, the nanocomposites also show great promise for the efficient delivery of native proteins with high generality. To the authors’ knowledge, this represents the first study pertaining to a facile methodology to prepare COF‐based insulin‐delivery nanocarriers for in vitro and in vivo therapeutic applications.