Facile Fabrication of Redox‐Responsive Covalent Organic Framework Nanocarriers for Efficiently Loading and Delivering Doxorubicin

Abstract

Covalent organic frameworks (COFs) as drug delivery systems have shown great promise, but their pharmaceutical applications are often limited by complex building blocks, tedious preparations, irregular shape, and uncontrolled drug release within target cells. Herein, a facile strategy is developed to prepare PEGylated redox‐responsive nanoscale COFs (denoted F68@SS‐COFs) for efficiently loading and delivering doxorubicin (DOX) by use of FDA‐approved Pluronic F68 and commercially available building blocks. The obtained F68@SS‐COFs with controlled size, high stability, and good biocompatibility can not only achieve a very high DOX‐loading content (about 21%) and very low premature leakage at physiological condition but can also rapidly respond to the tumor intracellular microenvironment and efficiently release DOX to kill tumor cells. Considering the readily available raw materials, simple preparation process, and desirable redox‐responsiveness, the strategy provided here opens up a promising avenue to develop well‐defined COFs‐based nanomedicines for cancer therapy.

pH and Redox Dual-Sensitive Covalent Organic Framework Nanocarriers to Resolve the Dilemma Between Extracellular Drug Loading and Intracellular Drug Release

“…A series of COFs has demonstrated great potential as a promising platform for effective loading and delivery of various drugs, because of their unique and attractive features (Fang et al, 2015 ; Bai et al, 2016 ; Vyas et al, 2016 ; Mitra et al, 2017 ; Wu and Yang, 2017 ; Hashemzadeh and Raissi, 2018 ; Zhao F. et al, 2018 ; Liu et al, 2020 ). In particular, the hydrazone-linked COFs based on Schiff-base chemistry exhibited a high stability under physiological conditions but acid-cleavable property within tumoral acid microenvironment, providing some unique advantages for biomedical, and pharmaceutical applications (Segura et al, 2016 ; Zhao F. et al, 2018 ).…”

“…COFs possess some desirable and unique features, including tunable pore geometry, large surface area, outstanding crystallinity, intrinsic adaptability, and excellent flexibility in molecular architecture, and functional design, thus exhibiting great potential for various applications (Sakaushi and Antonietti, 2015 ; Waller et al, 2015 ; Kandambeth et al, 2018 ; Song et al, 2019 ; Zhao et al, 2019 ). Recently, these porous frameworks opened up a new avenue for exciting opportunities in biomedical and pharmaceutical fields, especially for drug delivery (Fang et al, 2015 ; Bai et al, 2016 ; Vyas et al, 2016 ; Mitra et al, 2017 ; Wu and Yang, 2017 ; Hashemzadeh and Raissi, 2018 ; Zhao F. et al, 2018 ; Liu et al, 2020 ). The COFs as drug carriers have demonstrated some unique advantages.…”

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

“…Here, we will introduce the different kinds of methods to make the bread: COF-based oncotherapy examples. Till now, COFs have been used as drug delivery carriers, 221,[396][397][398][399][400][401][402][403] phototherapy reagents, 163,216,223,261,[404][405][406][407][408][409][410] and combination therapy platforms 161,162,220,[411][412][413][414][415] for tumor therapeutics ( Table 5).…”

A Versatile Method for Functionalization of Covalent Organic Frameworks via Suzuki–Miyaura Cross‐Coupling

“…Constructed by covalently linked organic molecules based on dynamic covalent chemistry and topological design principles, COFs feature low density, high stability, large porosity, and ordered, accessible channels [2, 3] . These characteristics endow COFs with potential applications in liquid‐phase adsorption, [4, 5] gas separation, [6, 7] energy storage materials, [8, 9] electronic devices, [10, 11] heterocatalysis, [12, 13] and drug delivery [14, 15] . By introducing functionalities into the defined channels, functional COFs can be obtained aiming at specific applications.…”