ROS self-generation and hypoxia self-enhanced biodegradable magnetic nanotheranostics for targeted tumor therapy

Abstract

Amelioration of solid tumor hypoxia is one of the promising therapeutic strategies for malignant tumor ablation. In particular, reactive oxygen species (ROS)-induced apoptosis has been proved to be an efficient tumor therapeutic approach, relying on advanced drug delivery or rapid production of ROS in the tumor region. However, the ROS generation is severely limited by tumor hypoxia. Herein, a new nanostructure based on biodegradable mesoporous magnetic nanocubes (MMNCs) is designed for ROS self-generation and self-enhancement magnetic thermotherapy. Typically, vitamin c (Vc) locked in MMNCs with phase-change materials (PCM) could be triggered by hyperthermia under an alternating magnetic field (AMF), serving as an original source for ROS (H₂O₂) generation. In addition, the MMNCs possess Fenton reagent-like activity in an acidic environment for ROS self-enhancement, which causes severe damage to tumor cells. The multifunctional nanotheranostics exhibits remarkable hyperthermia and enhanced ROS synergistic therapy efficiency. Furthermore, the nanoplatform demonstrates good biodegradability under acidic tumor microenvironment conditions. This finding highlights the great potential of Vc loaded magnetic nanoparticle composites as efficient agents for tumor therapy. It opens an avenue for the design of nanoformulations with ROS self-generation and self-enhancement for overcoming tumor hypoxia.