Cytotoxic effect of photodynamic liposome gel combined with trastuzumab on drugresistant breast cancer cells in vitro

Abstract

To evaluate the cytotoxic effect of photodynamic therapy (PDT) combined with targeted therapy using cross-linked liposomes and gels (Ce6-PC-Tmab@A-Gel) loaded with photosensitizer Chlorin (Ce6) and the tumor-targeting drug Trastuzumab (Tmab) in drug-resistant HER2+ breast cancer cells. Ce6-PC-Tmab liposomes were prepared using the thin-film hydration method. The general properties, encapsulation efficiency and near-infrared responsivity of the nanoparticles were evaluated. Ce6-PC-Tmab@A-Gel with a shear response was prepared by freeze drying and stirring crosslinking, and its microstructure was observed with scanning electron microscopy (SEM) and the shear response evaluated using a rheometer. The inhibitory effect of Ce6-PC-Tmab@A-Gel in drug-resistant HER2+ breast cancer SK-BR-3 cells was assessed with cytotoxicity assay (MTT assay) combined with near-infrared light. The particle size of Ce6-PC-Tmab was 239.7±9.7 nm and the potential was -2.03±0.09 mV. The entrapment efficiency of Tmab by Ce6-PC-Tmab liposomes was (40.22± 0.73)%. The prepared Ce6-PC-Tmab@A-Gel had a good shear response with excellent drug release characteristics under nearinfrared light, and increased intensity and duration of near-infrared light exposure enhanced Tmab release from the gel. Ce6-PC-Tmab@A-Gel was stable at room temperature and in a simulated tumor microenvironment (pH 6.25). Cytotoxicity assay (MTT) showed that Ce6-PC-Tmab@A-Gel combined with near-infrared light resulted in a survival rate of (31.37±1.73)% in SKBR-3 cells, much lower than that in the control group and other treatment groups (P < 0.01); the combined treatment also had a high efficiency of ROS production, and ROS release reached (22.36 ± 0.11)% after 2 min of near-infrared light exposure. The prepared Ce6-PC-Tmab@A-Gel has good near-infrared light response release characteristics to ensure effective targeted therapy with Tmab. The injectable gel system potentially allows long-term local drug release in the tumor to improve the treatment efficacy against drug-resistant breast cancer.