A Bacteriochlorin-Based Metal-Organic Framework Nanosheet Superoxide Radical Generator for Photoacoustic Imaging-Guided Highly Efficient Photodynamic Therapy.

Hypoxic tumor microenvironment is the bottleneck of the conventional photodynamic therapy (PDT) and significantly weakens the overall therapeutic efficiency. Herein, versatile metal-organic framework (MOF) nanosheets (DBBC-UiO) comprised of bacteriochlorin ligand and Hf(µ-O)(µ-OH) clusters to address this tricky issue are designed. The resulting DBBC-UiO enables numerous superoxide anion radical (O ) generation via a type I mechanism with a 750 nm NIR-laser irradiation, part of which transforms to high toxic hydroxyl radical (OH•) and oxygen (O) through superoxide dismutase (SOD)-mediated catalytic reactions under severe hypoxic microenvironment (2% O), and the partial recycled O enhances O generation. Owing to the synergistic radicals, it realizes advanced antitumor performance with 91% cell mortality against cancer cells in vitro, and highly efficient hypoxic solid tumor ablation in vivo. It also accomplishes photoacoustic imaging (PAI) for cancer diagnosis. This DBBC-UiO, taking advantage of superb penetration depth of the 750 nm laser and distinct antihypoxia activities, offers new opportunities for PDT against clinically hypoxic cancer.