Bifunctional Bismuth‐Based Layered Double Hydroxide Sonosensitizer for Magnetic Resonance Imaging‐Guided Sonodynamic Cancer Therapy

Novel inorganic sonosensitizers with excellent reactive oxygen species (ROS) generation activity and multifunctionality are appealing in sonodynamic therapy (SDT). Herein, amorphous bismuth (Bi)-doped CoFe-layered double hydroxide (a-CoBiFe-LDH) nanosheets are proposed via crystalline-to-amorphous phase transformation strategy as a new type of bifunctional sonosensitizer, which allows ultrasound (US) to trigger ROS generation for magnetic resonance imaging (MRI)-guided SDT. Importantly, a-CoBiFe-LDH nanosheets exhibit much higher ROS generation activity (≈6.9 times) than that of traditional TiO₂ sonosensitizer under US irradiation, which can be attributed to the acid etching-induced narrow band gap, high electron (e^-)/hole (h⁺) separation efficiency and inhibited e^-/h⁺ recombination. In addition, the paramagnetic properties of Fe ion endow a-CoBiFe-LDH with excellent MRI contrast ability, making it a promising contrast agent for T₂-weighted MRI. After modification with polyethylene glycol, a-CoBiFe-LDH nanosheets can function as a high-efficiency sonosensitizer to activate p53, MAPK, oxidative phosphorylation, and apoptosis-related signaling pathways, ultimately inducing cell apoptosis in vitro and tumor ablation in vivo under US irradiation, which shows great potential for clinical cancer treatment.