H. Haghighi, H. Heli, Ali Ketabi, R. Dehdari Vais, Parsa Faghani-Eskandarkolaei, Amid Rahi, M. Ziasistani, N. Sattarahmady
for cancerous (A549) and normal (MRC5) lung cells, respectively. In addition, laser light radiation following PGTCNA treatment resulted in disruption of mitochondrial membrane potential, photoporation, inhibition of cell migration, and alleviation of hypoxia-induced resistance in A549 cells. In both monolayer and tumorsphere models, treatment of A549 cells with PGTCNA in combination with 808-nm laser light and X-ray radiation (quadruple photodynamic/mild photothermal/radiodynamic/chemotherapy) synergistically reduced cell viability and enhanced ROS generation. In the tumorsphere model, the quadruple therapy triggered apoptosis in A549 tumorspheres. These findings suggested that PGTCNA acts as a promising photo/radiosensitizer to enhance the efficacy of photodynamic/mild photothermal/radiodynamic therapy of NSCLC, with the potential to overcome key challenges associated with radiotherapy.