A Biodegradable High-Efficiency Magnetic Nanoliposome Promotes Tumor Microenvironment-Responsive Multimodal Tumor Therapy Along with Switchable T₂ Magnetic Resonance Imaging

We explored the catalytic activity and magnetic resonance imaging (MRI) capacity of Cu-doped ultrasmall iron oxides with different doping ratios. Then, we screened a highly efficient ultrasmall active catalyst (UAC). Subsequently, a biodegradable magnetic nanoliposome was developed for multimodal cancer theranostics through pH-sensitive liposome coating of these UACs. Upon entering the body, the magnetic nanoliposomes significantly prolonged the metabolic time of UACs and promoted their accumulation in tumors. Then, the strong photothermal (PT) effect of the magnetic nanoliposome quickly ablated the tumor, showing promising PT therapy. Upon entering tumor cells, the magnetic nanoliposome rapidly degraded into many UACs and released chemotherapeutic drugs, contributing to chemotherapy. In addition, UACs not only catalyzed Fenton-type reaction to produce excessive reactive oxygen species (ROS) but also inhibited the synthesis of endogenous GSH by inactivating glutamyl cysteine ligase, contributing to cancer ferroptosis. Furthermore, the assembly-dissociation process of UACs showed the function of magnetic relaxation switches, significantly enhancing tumor MRI signal change, achieving a more accurate diagnosis of the tumor. Therefore, this magnetic nanoliposome splits into many UACs upon drug release and regulates the tumor microenvironment to overproduce ROS for enhanced synergistic tumor theranostics, which provides a strategy for developing next-generation magnetic catalysts with biodegradability and multimodal antitumor theranostics.