Injectable alginate-iridium complex hydrogel for sonodynamic therapy of breast cancer

Breast cancer remains one of the leading causes of cancer-related mortality in women worldwide, and sonodynamic therapy (SDT) has emerged as a promising non-invasive antitumor therapeutic modality. In this work, an injectable alginate (ALG) hydrogel loaded with an iridium complex (Ir958) was rationally fabricated for SDT-mediated suppression of breast cancer growth. The optimized composite hydrogel exhibited favorable injectability and excellent biocompatibility, while the loaded Ir958 effectively produced cytotoxic singlet oxygen upon ultrasound irradiation. In vitro biological evaluations demonstrated that the combined treatment of ALG/Ir958 hydrogel with ultrasound remarkably suppressed the proliferation of 4T1 breast cancer cells, triggered intracellular reactive oxygen species (ROS) overproduction, and ultimately facilitated tumor cell apoptosis. In vivo 4T1 xenograft experiments verified robust tumor suppression without major organ injury. Hypoxia-inducible factor 1α (HIF-1α) immunofluorescence and hematoxylin and eosin (H&E)/TUNEL staining further confirmed the ROS-mediated antitumor mechanism and tumor cell apoptosis. Collectively, this hydrogel is a safe and effective SDT platform for breast cancer with great clinical translation potential.