Design of Sonosensitizers Integrated with Resveratrol Motif for Synergetic Sonodynamic Therapy and Nuclear Factor Kappa B Transcription Suppression of Breast Cancer

作者：Yuanyuan Li, Ming Sun, Jie Yu, Wei Jiang, Wei Tian, Xin Chen, Silong Zhang, Huan He · 发表于：Journal of Medicinal Chemistry · 年份：2023 · DOI：10.1021/acs.jmedchem.2c01992 · 被引用次数：16 · 研究领域：Ultrasound and Hyperthermia Applications、Nanoplatforms for cancer theranostics、Photoacoustic and Ultrasonic Imaging

Sonodynamic therapy (SDT) has been recognized as a spatial–temporal and noninvasive modality for the treatment of deep-seated tumors. However, current sonosensitizers suffer from low sonodynamic efficacy. Herein, we reported the design of nuclear factor kappa B (NF-κB) targeting sonosensitizers ( TR1, TR2, and TR3 ) by integrating a resveratrol motif into a conjugated electron donor–acceptor (triphenylamine benzothiazole) skeleton. Among these sonosensitizers, TR2 with two resveratrol units in one molecule was the most potent for inhibiting NF-κB signaling. Owing to the synergy of high sonodynamic efficacy and NF-κB activation inhibition, TR2 displayed a remarkable sonocytotoxicity to MCF-7 breast cancer cells. Xenograft mice studies demonstrated that TR2 had excellent anticancer potency and biosafety. This study thus opens up a new avenue for the development of efficient organic sonosensitizers for cancer ablation.