A Regioselectively Oxidized 2D Bi/BiOx Lateral Nano‐Heterostructure for Hypoxic Photodynamic Therapy

Optoelectronic science and 2D nanomaterial technologies are currently at the forefront of multidisciplinary research and have numerous applications in electronics and photonics. The unique energy and optically induced interfacial electron transfer in these nanomaterials, enabled by their relative band alignment characteristics, can provide important therapeutic modalities for healthcare. Given that nano-heterostructures can facilitate photoinduced electron-hole separation and enhance generation of reactive oxygen species (ROS), 2D nano-heterostructure-based photosensitizers can provide a major advancement in photodynamic therapy (PDT), to overcome the current limitations in hypoxic tumor microenvironments. Herein, a bismuthene/bismuth oxide (Bi/BiOx)-based lateral nano-heterostructure synthesized using a regioselective oxidation process is introduced, which, upon irradiation at 660 nm, effectively generates 1 O2 under normoxia but produces cytotoxic •OH and H2 under hypoxia, which synergistically enhances PDT. Furthermore, this Bi/BiOx nano-heterostructure is biocompatible and biodegradable, and, with the surface molecular engineering used here, it improves tumor tissue penetration and increases cellular uptake during in vitro and in vivo experiments, yielding excellent oxygen-independent tumor ablation with 660 nm irradiation, when compared with traditional PDT agents.