Coordination-Mediated Glucose Oxidase Functionalization Endows UiO-66 with Aqueous Monodispersity for Self-Augmented Anticancer Therapy

Vollständiger Abstract

Worum geht es in dieser Arbeit?

Abstract Metal–organic frameworks show great potential for drug delivery, but issues such as poor aqueous dispersibility and structural complexity impose significant limitations on their further application. Herein, this study reports a novel surface modification strategy that utilizes the phenolic groups of the tyrosine residues on the endogenous glucose oxidase (GOx) molecule to coordinate with the zirconium elements in the UiO-66 structure. This strategy improves the dispersibility of UiO-66 in water through surface modification and achieves monodispersity. GOx-mediated starvation therapy promotes the production of H2O2, increasing the intracellular ROS contents in cancer cells and inducing apoptosis. Moreover, l-arginine is further loaded to construct a nanocarrier system for starvation/gas combination therapy. Both in vivo and in vitro experiments confirm the satisfactory therapeutic effects. In this work, the aqueous dispersion of UiO-66 was greatly improved for the first time via a noncovalent modification strategy. Moreover, a novel combination therapy based on starvation (mediated by bioendogenous GOx) and gas (from l-arginine) was realized. This strategy avoids the systemic toxicity associated with conventional chemotherapeutic drugs and demonstrates potent anticancer efficacy by significantly suppressing cancer cell proliferation and migration.