Abstract
The present study focuses on the photodynamic activity of zinc-substituted pheophorbide a against human endothelial cells. Previously, zinc pheophorbide a has been shown to be a very potent photosensitizer but also a strong albumin binder. Binding to albumin significantly reduces its availability to cancer cells, which may necessitate the use of relatively high doses. Here we show that zinc pheophorbide a is very effective against vascular endothelial cells, even in its albumin-complexed form. Albumin complexation increases the lysosomal accumulation of the drug, thus enhancing its efficiency. Zinc pheophorbide a at nanomolar concentrations induces endothelial cell death via apoptosis, which in many cases is considered a desirable cell death mode because of its anti-inflammatory effect. Additionally, we demonstrate that in comparison to tumor cells, endothelial cells are much more susceptible to photodynamic treatment with the use of the investigated compound. Our findings demonstrate that zinc pheophorbide a is a very promising photosensitizer for use in vascular-targeted photodynamic therapy against solid tumors, acting as a vascular shutdown inducer. It can also possibly find application in the treatment of a range of vascular disorders. Numerous properties of zinc pheophorbide a are comparable or even more favorable than those of the well-known photosensitizer of a similar structure, palladium bacteriopheophorbide (TOOKAD®).