2D materials in ultrasound-driven cancer therapies: Correlating material characteristics with therapeutic performance

Overcoming the limited penetration of phototherapies, ultrasound-based therapies (sonotherapies) have emerged as a promising cancer treatment due to their deep tissue reach and therapeutic efficacy. However, conventional organic sonosensitizers suffer from rapid clearance and poor solubility, limiting their effectiveness. In contrast, nanoscale sono-activatable agents, especially 2D materials, offer unique physicochemical properties, enhanced stability, and superior antitumor performance. Beyond acting as nanocarriers or passive supports, 2D materials actively participate in sonotherapy and enable the combination of multiple treatment modalities, improving therapeutic synergy. This review first outlines the fundamental principles and conventional applications of sonotherapy. It then focuses on recent advances in 2D materials as sonosensitizers and sonothermal agents, categorizing them based on structural and functional characteristics. We also discuss the mechanisms of ultrasound activation and how properties such as piezoelectricity, bandgap, and thermal conductivity contribute to treatment outcomes. Strategies to enhance these features—such as atomic doping, defect engineering, and heterojunction construction—are examined in depth. Finally, we highlight current progress, limitations, and challenges in translating 2D material-based sonotherapies into clinical practice. This review offers a timely and comprehensive perspective on the emerging role of 2D materials in sonotherapy and the critical gaps that must be addressed to enable their clinical adoption. • First comprehensive review on 2D materials in sonotherapies. • Physicochemical characteristics of the materials influence their performance. • Band gap issues can be improved by structural modification strategies. • Sonothermal therapy with 2D materials is a novel and underexplored field. • Key challenges and recent progress in 2D sonotherapy are critically reviewed.