Perylenequinones in photodynamic therapy: cellular versus vascular response

Photodynamic therapy (PDT) is a promising new modality in the treatment of cancers, which employs the interaction between a tumor-localizing photosensitizer and light of an appropriate wavelength to bring about molecular oxygen-induced cell death. We have investigated the efficacy of photosensitizers from the family perylenequinone, namely Hypericin, Hypocrellin A and B, in the treatment of cancer. These photosensitizers are known as potent second generation natural photosensitizers that have phototherapeutic advantages over the presently used porphyrins. We have studied the in vitro signaling mechanism involved in the photodynamic action following PDT in various human carcinoma cell lines. The difference of tumor cell death between two modes of action i.e., vascular- and cellular-mediated cell death, were evaluated in order to compare treatments that can efficaciously eradicate tumor in xenografts model. The antivascular effect of PDT was demonstrated in the chick chorioallantoic membrane (CAM) model. Tumor therapy based on targeting the vasculature of the tumor is indeed promising as demonstrated in the higher relative regression percentage of treated tumor compared to cellular targeted PDT. The favorable tumor response derived from short drug-light interval mediated PDT was primarily based on the differential uptake of the photosensitizer into tumor-associated vasculature as opposed to the cellular compartments of the tumor.