Cascade Nanozyme Comprising Pt-Coated Porphyrin Metal–Organic Frameworks Boosting Reactive Oxygen Species Generation for Sonodynamic Theranostics of a Tumor

Sonodynamic therapy (SDT) has demonstrated considerable potential in its noninvasive approach and ability to target tumors located deep within brain tissues (>10 cm). However, the effectiveness of this technique is hindered by tumor hypoxia (2% O 2 ), the abundance of the reactive oxygen species (ROS) scavenger glutathione (GSH), and the limited ROS generation capacity of the sonosensitizer. In light of these limitations, a cascade nanozyme comprising platinum (Pt)-coated porphyrin metal–organic frameworks (PCN-224(Fe)) modified with COOH-PEG was developed [Pt/PCN-224(Fe)/PEG, labeled as PFMP nanozyme] to enhance the toxicity of ROS. This nanozyme emulates the catalytic function of Pt in the decomposition of hydrogen peroxide (H 2 O 2 ) into O 2 for the purpose of alleviating tumor hypoxia. Additionally, it replicates the function of glutathione peroxidase (GPX) by utilizing iron (Fe 3+ ) to reduce the overexpression of GSH. These two mechanisms act in concert to amplify the generation of ROS. They achieve this by enhancing O 2 production and impairing the capacity of GSH to scavenge ROS, thereby synergistically potentiating the toxicity of ROS. In vitro and in vivo studies have demonstrated evidence for efficient ROS generation, resulting in a significant 6-fold reduction in tumor volume compared to the control groups and achieving an impressive 80% survival rate 30 days after treatment.