Nanosonosensitizer Optimization for Enhanced Sonodynamic Disease Treatment

Low-intensity ultrasound-mediated sonodynamic therapy (SDT), which, by design, integrates sonosensitizers and molecular oxygen to generate therapeutic substances (e.g., toxic hydroxyl radicals, superoxide anions, or singlet oxygen) at disease sites, has shown enormous potential for the effective treatment of a variety of diseases. Nanoscale sonosensitizers play a crucial role in the SDT process because their structural, compositional, physicochemical, and biological characteristics are key determinants of therapeutic efficacy. In particular, advances in materials science and nanotechnology have invigorated a series of optimization strategies for augmenting the therapeutic efficacy of nanosonosensitizers. This comprehensive review systematically summarizes, discusses, and highlights state-of-the-art studies on the current achievements of nanosonosensitizer optimization in enhanced sonodynamic disease treatment, with an emphasis on the general design principles of nanosonosensitizers and their optimization strategies, mainly including organic and inorganic nanosonosensitizers. Additionally, recent advancements in optimized nanosonosensitizers for therapeutic applications aimed at treating various diseases, such as cancer, bacterial infections, atherosclerosis, and autoimmune diseases, are clarified in detail. Furthermore, the biological effects of the improved nanosonosensitizers for versatile SDT applications are thoroughly discussed. The review concludes by highlighting the current challenges and future opportunities in this rapidly evolving research field to expedite its practical clinical translation and application.