Bifunctional Bismuth-Based Layered Double Hydroxide Sonosensitizer for Magnetic Resonance Imaging-Guided Sonodynamic...

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.