Polymer–Covalent Organic Frameworks Composites for Glucose and pH Dual‐Responsive Insulin Delivery in Mice

Abstract

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.

In vivo oral insulin delivery via covalent organic frameworks

“…It is anticipated that upon loading with insulin, the periodicity in the TTA-DFP-nCOF layers is affected to accommodate insulin molecules, thus losing crystallinity. [57][58][59][60] When the TTA-DFP-nCOF was loaded with a reduced quantity of insulin (30% loading capacity, ESI †), the PXRD pattern showed the presence of 2q ¼ 4.9 and 25.6 peaks, although their intensities decreased signicantly compared to those of the pristine nCOF, conrming our hypothesis. The uniformity of TTA-DFP-nCOF/insulin is evident from AFM analysis and increased to 12 nm upon insulin encapsulation compared to that of the pristine nCOF (Fig.…”

Emerging porous organic polymers for biomedical applications

“…Then, a brief discussion on their synthetic strategies and functionalization approaches is provided. Subsequently, a detailed description is provided on the applications of POPs in diverse biomedical fields, including drug delivery, 76,101–116 biomacromolecule encapsulation, 117–129 photodynamic and photothermal therapy, 130–147 biosensing, 69,148–151 bioimaging, 152–155 antibacterial, 156–161 bioseparation, 162 and others, as shown in Fig. 2.…”

Nanoscale covalent organic frameworks as theranostic platforms for oncotherapy: synthesis, functionalization, and applications

“…Host-guest encapsulation is a versatile and effective modication strategy to endow COFs with more functions, which utilizes accessible and permanent pores of COFs to capture guest molecules, including a variety of functional inorganic molecules, [382][383][384][385][386] organic molecules, [387][388][389] and even biological macromolecules. [390][391][392][393] The structural basis of host-guest encapsulation is the pores of COFs, which have unique characteristics. 394,395 First, the pores of COFs have a precise polygonal reticular structure with well-dened angles.…”