Abstract
In this study, the in vitro photodynamic therapy (PDT) activity of two zinc phthalocyanines (ZnPc1 and ZnPc2) was systematically examined in human umbilical vein endothelial cells, focusing on PDT-induced cytotoxicity, reactive oxygen species (ROS) generation, and inhibition of angiogenic processes. Both the ZnPcs demonstrated minimal cytotoxicity in the absence of light, confirming their safety as photosensitizers. ZnPc-PDT led to significant cell death via apoptosis. ZnPc1 exhibited enhanced ROS generation, particularly at elevated concentrations. Furthermore, ZnPc1-mediated PDT showed more pronounced inhibition of endothelial cell migration, invasion, and capillary-like tube formation than ZnPc2. Wound-healing assays revealed a substantial delay in human umbilical vein endothelial cell (HUVEC) migration following ZnPc1-PDT, which also displayed a more significant inhibition of VEGF-induced directional migration and invasion. Endothelial tube formation was more effectively disrupted by ZnPc1-PDT, even at lower concentrations, compared to ZnPc2. Collectively, these findings highlight the superior cytotoxic and anti-angiogenic properties of ZnPc1 compared with ZnPc2, highlighting its potential as a highly effective photosensitizer for photodynamic therapy. The ability of ZnPc1 to simultaneously target tumor cells and disrupt angiogenesis establishes it as a potent candidate for integrated cancer therapies that combine both antitumor and antiangiogenic strategies, offering a more effective approach to combat cancer progression.