Strategies to Reverse Hypoxic Tumor Microenvironment for Enhanced Sonodynamic Therapy

Sonodynamic therapy (SDT) has emerged as a highly effective modality for the treatment of malignant tumors owing to its powerful penetration ability, noninvasiveness, site-confined irradiation, and excellent therapeutic efficacy. However, the traditional SDT, which relies on oxygen availability, often fails to generate a satisfactory level of reactive oxygen species because of the widespread issue of hypoxia in the tumor microenvironment of solid tumors. To address this challenge, various approaches are developed to alleviate hypoxia and improve the efficiency of SDT. These strategies aim to either increase oxygen supply or prevent hypoxia exacerbation, thereby enhancing the effectiveness of SDT. In view of this, the current review provides an overview of these strategies and their underlying principles, focusing on the circulation of oxygen from consumption to external supply. The detailed research examples conducted using these strategies in combination with SDT are also discussed. Additionally, this review highlights the future prospects and challenges of the hypoxia-alleviated SDT, along with the key considerations for future clinical applications. These considerations include the development of efficient oxygen delivery systems, the accurate methods for hypoxia detection, and the exploration of combination therapies to optimize SDT outcomes.