Engineering Microwave-Activatable Nanoenergic Converters with Energy Cascade Structures for On-Demand Microwave Dynamic Therapy

Microwave dynamic therapy (MDT) has emerged as a promising therapy for cancer treatment. However, its therapeutic efficacy is constrained by limited microwave (MW) energy density and suboptimal MW absorption capacity of conventional MW sensitizers. To address these challenges, we engineer Ti₃C₂@CoFeMOF@CaO₂ nanoenergic converters (MMC-NCs) to augment reactive oxygen species (ROS) generation. Through enhancement of dielectric loss, the MW absorption capacity of MMC-NCs is promoted. Importantly, MMC-NCs overcome intrinsic MW energy limitations via a coupled energy cascade strategy. Under MW irradiation, CoFeMOF-induced hyperthermia establishes a thermal gradient across the Ti₃C₂/CoFeMOF heterostructure, creating a built-in electric field via the thermoelectric effect of Ti₃C₂. Experimental and density functional theory (DFT) analyses demonstrate that the built-in electric field promotes electron-hole separation and elevates the electron density in CoFeMOF, enabling electron-mediated ROS production (·OH and ¹O₂) via reacting with absorbed H₂O₂/O₂. In vitro and in vivo validations confirm that MMC-NCs effectively inhibit tumor growth and eliminate <i>Staphylococcus aureus</i> (<i>S. aureus</i>) in 4T1 tumor-bearing mice, where <i>S. aureus</i> is known to aggravate the malignant progression of breast cancer. Collectively, this innovative MMC-NCs not only optimize MW energy utilization but also overcome the intrinsic energy density limitations, making a major step forward in enhancing MDT efficacy for antitumor and antibacterial applications.