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

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.