Multifunctional Porphyrin‐Based Sonosensitizers for Sonodynamic Therapy

Abstract Sonodynamic therapy (SDT), as a promising non‐invasive therapeutic modality combining ultrasound (US) and sonosensitizers to produce cytotoxic reactive oxygen species (ROS) for treating deep‐seated tumors, has received increasing attention in recent years. Porphyrins are multifunctional organic materials, which can be excited both by light and US to produce ROS and possess various fascinating features, including controllable synthetic processes, excellent biodegradability, low cytotoxicity without light or US. Nevertheless, their poor water solubility, skin‐photosensitive toxicity, and insufficient target specificity hinder their clinical applications as sonosensitizer. Although the target specificity issue may be improved by using nanoparticle carriers, and the SDT efficacy can be enhanced by combining with other therapeutic modalities, such combination therapy makes it more confusing about the true mechanism of SDT. This review will focus on the following points: 1) Why are porphyrin‐based sonosensitizers considered the most promising sonosensitizer for clinical applications of SDT? 2) Recent progress in the development of multifunctional porphyrin‐based sonosensitizers. 3) What new insight has been gained on the mechanism of SDT in recent years? 4) The development trend of designing more efficient multifunctional porphyrin‐based sonosensitizers and existing challenges. Finally, future perspective of practical clinical applications of SDT based on multifunctional porphyrin‐based sonosensitizers will be discussed.