Defect-engineered metal-organic framework as a universal platform for theranostic applications

Rational design of nanocarriers as specific multidrug co-delivery systems to overcome the complex disease microenvironment still remains a critical challenge in precision nanomedicine. In this study, using dicarboxyl-functionalized indocyanine green (Bis-COOH-ICG) as an auxiliary ligand coordinated with Zr₆ clusters, a defect-engineered and functionalized metal-organic framework (Fun-MOF) with hierarchically micro/mesoporous architectures was successfully developed for tumor photothermal/photodynamic combination therapy (PTT/PDT) as well as photoacoustic/fluorescence dual-modal imaging (PAI/FI). And, the hierarchical Fun-MOF enables efficient co-encapsulation of HSP90 inhibitor 17-AAG and catalase (CAT), thus receiving potent antitumor therapy by inhibiting HSP90 overexpression and scavenging hydrogen peroxide to remodel the hypoxic tumor microenvironment. Additionally, owing to the robust coordination chemistry between Zr₆ clusters and carboxyl groups, the defective Fun-MOF also can incorporate other carboxyl-containing small-molecule therapeutics during MOF preparation, making it a universal platform for diverse theranostic applications.