Engineered Metal-Organic Frameworks for Sonodynamic Therapy: from Coordination Chemistry to Acoustic-ROS Transduction

Sonodynamic therapy (SDT) has emerged as a noninvasive therapeutic strategy for deep-seated tumors. However, its clinical translation remains substantially limited by the inherently low energy density and transient nature of ultrasound, which lead to insufficient and unsustained reactive oxygen species (ROS) generation within the therapy-resistant tumor microenvironment (TME). In this review, we introduce the concept of MOFs as precision sonoreactors, wherein hierarchical coordinative architectures orchestrate acoustic energy capture, charge transduction, and catalytic ROS evolution within a single materials platform. Within this framework, the SDT process is deconstructed into a sequence of programmable energy conversion events, including cavitation-mediated energy focusing, acoustoelectric charge separation via photonic or electromechanical pathways, and subsequent catalytic transformation into lineage-specific ROS. By elucidating the underlying physicochemical mechanisms, we systematically reveal how the structural versatility of MOFs governs ROS generation and modulation. Beyond primary ultrasound activation, we further highlight the ability of MOFs to overcome TME-associated barriers, reprogram the local microenvironment, and enable synergistic interactions with complementary therapeutic modalities. By shifting the paradigm from empirical optimization to mechanism-driven design, this review establishes a unified theoretical framework and delineates fundamental principles for the development of next-generation sonodynamic platforms.