Search

[Display omitted] • A novel inorganic sonosensitizer (a-Mn-CoMo-LDH) was proposed for MRI-guided SDT. • Acid etching of Mn-CoMo-LDH successfully activated its ROS generation activity. • Doped Mn4+ decomposed H 2 O 2 into O 2 to alleviate the hypoxic tumor microenvironment. • Mn4+ consumed GSH to reduce its clearance of ROS and also generated Mn2+ for MRI. Sonodynamic therapy (SDT) has attracted increasing attention owing to its superior tissue penetration compared with other therapies. However, the development of multifunctional sonosensitizers with imaging capability and high production efficiency of reactive oxygen species (ROS) is still a challenge for current sonodynamic cancer therapy. Herein, we report the design and preparation of amorphous 2D Mn-doped CoMo-layered double hydroxide (a-Mn-CoMo-LDH) nanosheets (NSs) through acid etching-induced crystalline-to-amorphous phase transformation as a highly active nano-agent for magnetic resonance imaging (MRI)-guided SDT. The a-Mn-CoMo-LDH NSs exhibit superior ROS production capacity compared with amorphous CoMo-LDH NSs (∼1.3 times) and crystalline Mn-CoMo-LDH NSs (∼3.9 times) under ultrasound (US) irradiation, which is ∼ 9.9 times of the previously reported TiO 2 sonosensitizer. The doped Mn4+ in the a-Mn-CoMo-LDH NSs can not only decompose H 2 O 2 into O 2 to alleviate the hypoxia level in tumor microenvironment (TME), but also consume glutathione (GSH) to reduce its clearance of ROS, promoting the SDT performance synergistically. Importantly, the GSH consumption can partially reduce the Mn4+ to Mn2+ within the tumors, which can serve as an agent for T 1 -weighted MRI, thus endowing the a-Mn-CoMo-LDH NSs with excellent MRI capability. Therefore, the as-prepared a-Mn-CoMo-LDH NSs with polyethylene glycol modification can be used as an efficient nano-agent for MRI-guided SDT, which can effectively achieve apoptosis of cancer cells in vitro and eradication of tumors in vivo under US irradiation. [ABSTRACT FROM AUTHOR]