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

Abstract Objective: Due to its significant tissue penetration, sonodynamic therapy (SDT) is rapidly becoming a viable alternative to traditional photodynamic therapy. However, the therapeutic efficacy of a single SDT treatment is constrained by the prolonged hypoxia of the tumor, rendering it ineffective for disease cure. This study employed SDT in conjunction with nitric oxide (NO) gas to induce apoptosis and ferroptosis in hepatocellular carcinoma (HCC) cells, aiming to facilitate cancer treatment.
Approach: In this work, the synthesis of TAPP@NBs involved the encapsulation of 5,10,15,20-Tetrakis (4-aminophenyl) porphyrin within a hydrated phospholipid film. Structural and morphological properties of the nanoparticles were analyzed using dynamic light scattering and transmission electron microscopy. In vitro, the anticancer cytotoxicity of TAPP@NBs was examined using HepG2 and HUH7 hepatoma cell lines. Identification of TAPP@NBs mediated SDT for HCC therapy through the mitochondrial pathway was achieved by staining with 2, 7-dichlorodihydrofluorescein diacetate (DCFH-DA) and 5,5', 6,6'-tetrachloro-1, 1', 3,3'-tetraethylimidacloprid iodide (JC-1). Quantification of cell viability and apoptosis was conducted using CCK-8 and flow cytometry. Evidence of iron death was established using the glutathione (GSH) metabolism assay and malondialdehyde (MDA) assay. The cellular migratory capacity was assessed using a transwell assay.
Main results: TAPP@NBs could effectively generate deadly amounts of reactive oxygen species (ROS) through ultrasonic irradiation. Under ultrasonography, nitrosoglutathione (GSNO) could serve as a NO donor and contribute to gas treatment, so significantly improving the effectiveness of SDT. Significant reductions in HCC cell activity and migration ability were observed after the combination of SDT with NO gas therapy.
Significance: SDT in conjunction with NO gas therapy can effectively induce apoptosis and ferroptosis in HCC cells. This study presents a novel approach for the optimization of tumor treatment.