Glutathione and acid dual-responsive bismuth-based nanosensitizer for chemo-mediated cancer sonodynamic therapy.

Guobo Chen, Jing Ping, Jun Du, Linghao Zhao, Yuhao Li, Hui Liu
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Abstract

Chemotherapeutic agents hold significant clinical potential in combating tumors. However, delivering these drugs to the tumor site for controlled release remains a crucial challenge. In this study, we synthesize and construct a glutathione (GSH) and acid dual-responsive bismuth-based nano-delivery platform (BOD), aiming for sonodynamic enhancement of docetaxel (DTX)-mediated tumor therapy. The bismuth nanomaterial can generate multiple reactive oxygen species under ultrasound stimulation. Furthermore, the loading of DTX to form BOD effectively reduces the toxicity of DTX in the bloodstream, ensuring its cytotoxic effect is predominantly exerted at the tumor site. DTX can be well released in high expression of GSH and acidic tumor microenvironment. Meanwhile, ultrasound can also promote the release of DTX. Results from bothin vitroandin vivoexperiments substantiate that the synergistic therapy involving chemotherapy and sonodynamic therapy significantly inhibits the growth and proliferation of tumor cells. This study provides a favorable paradigm for developing a synergistic tumor treatment platform for tumor microenvironment response and ultrasound-promoted drug release.

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用于化疗介导的癌症声动力疗法的谷胱甘肽和酸双响应铋基纳米敏化剂。
化疗药物在抗击肿瘤方面具有巨大的临床潜力。然而,如何将这些药物输送到肿瘤部位进行控释仍是一项关键挑战。在这项研究中,我们合成并构建了一种谷胱甘肽(GSH)和酸双响应铋基纳米递送平台(BOD),旨在通过声动力学增强多西他赛(DTX)介导的肿瘤治疗。铋纳米材料在超声刺激下可产生多种活性氧(ROS)。此外,负载 DTX 形成 BOD 能有效降低 DTX 在血液中的毒性,确保其细胞毒性作用主要在肿瘤部位发挥。在高表达 GSH 和酸性肿瘤微环境中,DTX 可以很好地释放。同时,超声也能促进 DTX 的释放。体外和体内实验结果证实,化疗与超声动力疗法(SDT)的协同治疗能显著抑制肿瘤细胞的生长和增殖。这项研究为开发肿瘤微环境反应和超声促进药物释放的协同肿瘤治疗平台提供了一个有利的范例。
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