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

Abstract 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 6 (µ 3 ‐O) 4 (µ 3 ‐OH) 4 clusters to address this tricky issue are designed. The resulting DBBC‐UiO enables numerous superoxide anion radical (O 2 −• ) 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 2 ) through superoxide dismutase (SOD)‐mediated catalytic reactions under severe hypoxic microenvironment (2% O 2 ), and the partial recycled O 2 enhances O 2 −• 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.