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

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.