Convertible ROS Nanogenerator/Eliminator for Enhanced Tumor Photothermal Therapy with Reduced Inflammatory Response

Abstract Photothermal therapy (PTT), as an innovative optical tumor treatment strategy, is characterized by its minimal invasiveness, high selectivity, long‐lasting efficacy, and high safety, and has attracted widespread attention. However, in order to effectively kill cancer cells, a higher local temperature is very necessary, which inevitably results in severe stress responses and cell death, thereby triggering harmful inflammation. Additionally, achieving effective controlled release of drugs in the tumor microenvironment to reduce systemic side effects is still a major challenge. Herein, an intelligent nanoplatform is first reported, which featured sulfide iron (FeS) nanosheets as the core, loaded with perfluorohexane (PFH), and skillfully coated with polydopamine (PDA). It can serve as a generator of reactive oxygen species (ROS) in the tumor microenvironment to induce tumor cell ferroptosis, further intensifying PTT, and as a ROS eliminator in normal tissue to effectively control the undesired inflammatory response during PTT, achieving a differential treatment strategy between tumor and surrounding normal tissue. Meanwhile, the combination of ultrasound‐targeted microbubble destruction (UTMD) technology significantly enhanced the local penetration and release of the drug. Overall, systemic delivery of FeS/PFH@PDA combined UTMD can achieve precise and efficient synergistic therapy for tumors and demonstrate outstanding ultrasound and MR dual‐mode imaging performance.