pH-Responsive Covalent Organic Framework-based Nanocarrier for Targeted Delivery of Cancer Therapeutics

Covalent organic frameworks (COFs) are an emerging class of porous organic polymers with a broad spectrum of possible applications because of their large void spaces and modular pores. Despite excellent cytocompatibility, porosity, and biodegradability of COFs, their practical implementations in nanomedicine have been limited due to low water dispersibility and poor processability into nanodimensions. There are limited reports on nanoscale covalent organic frameworks, which can exhibit excellent drug loading capacity and pH-responsive drug release. Herein, a water-dispersible 2D COF-based nanocarrier is reported for pH-responsive targeted delivery of therapeutics (doxorubicin) to cancer cells. Particularly, a hydrolytically susceptible boronate ester-based covalent organic framework (COF-5) is supramolecularly stabilized with an amphiphilic polymer, Pluronic F127 (PLU), to obtain COF-PLU nanoparticles with a size of ~185 nm and a thickness of ~25 nm. A high doxorubicin loading in the COF-based nanocarrier (>90% drug loading efficiency and ~35% drug loading capacity) and pH-responsive drug release are observed. Furthermore, the surface modification of Dox-loaded polymer-stabilized COF-5 with hyaluronic acid demonstrates selective delivery of doxorubicin to cancer cells. Our study demonstrates a facile strategy for developing a pH-responsive COF-based nanocarrier with excellent drug-loading capacity for targeted delivery of therapeutics to cancer cells.