Barium Titanate Incorporated Chitosan/Hyaluronic Acid Hydrogel Enables Piezocatalytic Therapy against Breast Cancer

Breast cancer is a highly prevalent malignancy worldwide. Current clinical treatments including surgery, chemotherapy and phototherapy still suffer from inevitable limitations, such as invasive trauma, systemic side effects, drug resistance and insufficient immune activation, which restrict further therapeutic improvement. To address these drawbacks, an injectable chitosan/hyaluronic acid/barium titanate (CS/HA/BTO) composite hydrogel was fabricated in this work for ultrasound-controlled piezocatalytic breast tumor therapy. The CS/HA hydrogel matrix exhibits excellent adhesion, self-healing performance and shear-thinning injectability, and achieves pH-responsive sustained release of BTO nanoparticles. After systematic screening, 200 μg/mL was confirmed as the optimal and biosafe working concentration. In vitro cellular experiments demonstrated that ultrasonic excitation enables BTO to generate abundant reactive oxygen species via piezocatalysis, which efficiently kills MCF-7 breast cancer cells. Moreover, piezocatalytic stimulation induced distinct expression changes among TIPE genes associated with tumor apoptosis regulation. Different from conventional tumor treatment modes, this ultrasound-responsive piezocatalytic hydrogel avoids drug-related toxicity, providing a promising in-vitro therapeutic platform for localized breast cancer targeted therapy.