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

Abstract

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.

Molecular Sonosensitizer-Loaded Polymer Nanomicelle for Ultrasound-Based Cell Therapy via Singlet Oxygen Generation

“…Chemical structures and optical properties of molecular sonosensitizers that are used in this study are shown in Figure . They are selected based on the existing literature including the most commonly studied one to the least studied one. − They include chlorine e6, protoporphyrin IX, rose bengal, curcumin, IR780 iodide, emodin, doxorubicin, levofloxacin, tannic acid, epigallocatechin gallate (EGCG), and catechin. We have selected tannic acid, EGCG, and catechin due to their well-known therapeutic applications.…”

“…Ultrasound has a great potential for sonodynamic therapy with the wireless treatment option in a range of human diseases. − This therapeutic approach requires sound-responsive materials, commonly known as sonosensitizers. − Well-known sonosensitizers include microbubbles, piezoelectric nanoparticles, and some selected organic small molecules. − Among them, microbubbles are the most popular due to their high sound-responsive property, although their large size restricts the in vitro / in vivo targeting options. − Similarly, piezoelectric nanoparticles are promising, although their design with high sound-responsive performance is challenging. − In contrast, organic small molecule-based sonosensitizers are attractive due to their clear chemical structure and smaller size. − However, they must have specific functional groups to offer the sonodynamic activity, and a clear understanding of the origin of such activity is yet to be established . Moreover, small molecule sonosensitizers are hydrophobic/organic in nature with low water solubility and low cell/tumor specificity and have a short circulation time in physiological conditions …”