In vitro activity: Verteporfin is about four times more efficient in absorbing light at wavelengths that penetrate tissues best (i.e., around 700 nm) and thus provides a much higher cytotoxic effect than hematoporphyrin (10 times more in human adherent cell lines). Verteporfin is lipophilic and is more readily taken up by malignant or activated cells, compared with normal or resting cells. Verteporfin binds with LDL to form a complex, which is then taken up into proliferating cells (e.g., neovascular endothelial cells) probably via LDL receptors and endocytosis. Verteporfin therapy achieves complete angiographic occlusion of the neovascular compartment by thrombosis of vascular channels, following selective endothelial damage. Verteporfin therapy selectively induces reproducible and isolated choriocapillary occlusion without alteration of overlying photoreceptors or ganglion cells, as shown by light and electron microscopy. Verteporfin conbined with light rapidly exhibits apoptotic changes reflected by caspase-3 and caspase-9 activation and PARP cleavage in HL-60 cells, changes that are blocked by the general caspase inhibitor ZVAD.fmk.

Cell Assay: PDX cells co-cultured with S17 cells are treated with 16 combinations of verteporfin (60 nM, 120 nM, 180 nM, and 240 nM) and dasatinib (12 nM, 24 nM, 36 nM, and 48 nM). The viabilities of cells treated with each combination are measured after 48 h using FACS Aria flow cytometer. In order to estimate drug interaction between verteporfin and dasatinib, a normalized isobologram and fraction affectedcombination index (CI) plot are made using CompuSyn software. CI values greater than 1.0 indicated antagonistic effects, equal to 1.0 additive effects, and below 1.0 synergistic effects.

Surv Ophthalmol. 2000 Nov-Dec;45(3):195-214; Blood. 2000 Jan 1;95(1):256-62.