Tumor microenvironment-responsive nanoregulator CoMnMOF superparticles for enhanced microwave dynamic therapy via multi-pronged amplification of reactive oxygen species

Microwave dynamic therapy (MDT) is promising in tumor therapy by generation of toxic reactive oxygen species (ROS), whose therapeutic efficacy is severely compromised by hypoxia and the antioxidant defense in the tumor microenvironment (TME). To address these bottlenecks, we designed a multifunctional nanoregulator CoMnMOF@Apatinib@l-menthol@RBC-HA (denoted as CMALRH) to achieve enhanced MDT via a multi-pronged ROS amplification strategy. We demonstrated that the enhanced ROS generation is attributed to the up-regulate O₂ level, down-regulate vascular endothelial growth factor (VEGF) expression and deplete glutathione (GSH). Meanwhile, CMALRH is verified to perform superior microwave (MW) thermal effect, thus remarkably potentiating the efficacy of anti-tumor therapy. The experiments in vitro and in vivo confirmed the enhanced MDT in combination with microwave thermal therapy can successfully inhibit the proliferation of breast cancer. This TME based ROS amplification strategy provides an avenue for the development of remarkably high efficiency MDT and MW thermal therapy.