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

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 both in vitro and in vivo experiments 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.