A covalent organic framework-based multifunctional therapeutic platform for enhanced photodynamic therapy via catalytic cascade reactions

Abstract

Utilizing the unique tumor microenvironment (TME) to conduct chemical reactions for cancer treatment becomes a hot topic recently. Nevertheless, single chemical reaction in TME is often restricted by scanty reaction substrates and slow reaction rate. Meanwhile, the toxic substances produced by the reactions are usually not enough to kill cancer cells. Herein, using covalent organic frameworks (COFs) as the template, Au nanoparticles (Au NPs) were subsequently grown on the surface of the COF, then a thin layer of manganese dioxide (MnO2) was coated over the material, and finally hyaluronic acid (HA) was introduced to improve the biocompatibility. The resultant product, named COF-Au-MnO2, was involved in several processes to form cascade reactions in the TME. Specifically, under hypoxic conditions, COF-Au-MnO2 could react with intratumoral H2O2 to produce O2 to enhance the type II photodynamic therapy (PDT), and Au NPs could decompose glucose to promote starving-like therapy. Besides, starving-like therapy can also produce H2O2 to increase O2 production. Simultaneously, MnO2 can consume glutathione (GSH) to enhance the antitumor efficacy, and the released Mn2+ could be used for T1-weighted magnetic resonance imaging (MRI). Both in vitro and in vivo experiments had proven excellent cancer cell killing effect and antitumor efficacy of COF-Au-MnO2via such a cycle-like process.