TAPP@NBs combined with GSNO to enhance the anti-liver cancer effect of sonodynamic therapy

Sonodynamic therapy (SDT) is a viable alternative to traditional photodynamic therapy owing to its ability to penetrate tissue. However, the therapeutic efficacy of a single SDT treatment is constrained by the prolonged hypoxia of the tumor, rendering SDT ineffective for treating disease. SDT was used in conjunction with nitric oxide (NO) gas in this study to induce apoptosis and ferroptosis in hepatocellular carcinoma (HCC) cells for treating cancer treatment. We synthesized 5,10,15,20-tetra (4-aminophenyl) porphyrin nanobubbles (TAPP@NBs) for the SDT treatment. S-nitroso glutathione (GSNO) was used as an NO gas donor. The<i>in vitro</i>anticancer effect of the combined treatment was examined using HepG2 and HUH7 hepatoma cell lines. Reactive oxygen species and NO were examined using 2,7-dichlorodihydrofluorescein diacetate and 3-amino,4-aminomethyl-2',7'-difluorescein diacetate staining, respectively. Cell proliferation and apoptosis were analyzed using CCK-8 and flow cytometry, respectively. Ferroptosis was evidenced using glutathione and malondialdehyde assays. The cellular migratory capacity was assessed using a Transwell assay. TAPP@NBs can serve as a sonosensitizer for the SDT. GSNO serves as an NO donor under ultrasound and contributes to gas treatment, considerably increasing SDT efficacy. HCC cell proliferation and migration were considerably lower after combined SDT and NO gas therapy. Combined SDT and NO gas therapy induced apoptosis and ferroptosis in HCC cells. This paper describes a novel approach for optimizing tumor treatment.