An Ultrasound-Excitable Aggregation-Induced Emission Dye for Enhanced Sonodynamic Therapy of Tumors

Ultrasound (US)-triggered sonodynamic therapy (SDT) can significantly solve the problem of tissue penetrability of light of photodynamic therapy (PDT) that has long vexed physicians in clinics. However, there is a great shortage of sonosensitizers for SDT. Currently, several photosensitizers and their derivatives have been reported for SDT but these dyes are usually quenched when aggregated due to aggregation-caused quenching (ACQ) effect. In this work, aggregation-induced emission (AIE) dye (TTMN) assembled nanoparticles (S-AIE) are synthesized and employed as sonosensitizers for enhanced SDT due to the unique properties of the AIE dye and the deep tissue penetration of ultrasound. Results show that S-AIE can generate potent singlet oxygen (¹O₂) under US irradiation to induce cancer cells apoptosis and clearly inhibit tumor growth in vitro and in vivo. In particular, the intrinsic fluorescence of AIE dye can guide the procedure of SDT. To the best of current knowledge, this is the first demonstration of AIE dyes being used as sonosensitizers for SDT and importantly, this work could inspire other more efficient AIE dyes for being used as sonosensitizers for SDT of deep-seated tumors.