Microwave-triggered organic sensitizer for synergistic dynamic/thermal therapy of osteosarcoma

Osteosarcoma (OS) is an aggressive malignant tumor with high recurrence and metastatic potential, primarily affecting adolescents. Despite the standard clinical "sandwich" treatment regimen, patient survival rates have remained stagnant. Microwave ablation (MWA), known for its rapid heating and strong tissue penetration, has emerged as a viable therapeutic strategy for bone tumors. However, MWA poses challenges, particularly the potential for iatrogenic damage to adjacent healthy tissues and the concern that inappropriate energy delivery parameters may paradoxically stimulate neoplastic progression. In this study, microwave-triggered organic nanoparticles, termed ATT, were synthesized via a spontaneous [2 + 2] cycloaddition-cycloreversion (CA-CR) reaction. Findings from cell-based assays and animal studies indicated that ATT effectively generated reactive oxygen species (ROS) and produced heat under microwave (MW) irradiation, achieving a remarkable tumor inhibition rate of 95%. Owing to its unique donor-acceptor (D-A) structure and twisted molecular configuration, ATT facilitates efficient charge transfer under MW irradiation. The process generates electron-hole pairs, enhancing ROS production and enabling an effective microwave dynamic therapy (MDT) effect. Moreover, ATT acts as a polar molecule that efficiently absorbs MW and generates heat through resonance, thereby potentiating the therapeutic performance of microwave thermal therapy (MTT). This study presents a novel microwave-triggered organic nanomaterial that integrates MTT and MDT, offering a prospective therapeutic intervention for OS.