Development of tumor vascular endothelium targeted liposomes containing zinc phthalocyanine for application in photodynamic therapy

Photodynamic therapy (PDT) is a modality for the removal of solid tumors, in which a photosensitized tumor is irradiated with intense light to activate the photosensitizer and induce local hyperoxidative stress. The production of reactive molecular species at the tumor site results in massive tumor cell death, vascular shutdown, and a prolonged antitumor immune response. Promising results have been achieved in the application of PDT to terminal perihilar cholangiocarcinoma patients, although it was found that the morbidity associated with non-specific association of photosensitizers does not weigh up to the treatment benefits. Hence, patients may benefit from a photosensitization strategy that selectively increases the photosensitizer concentration in the tumors. The use of cationic liposomes may be a promising method to achieve this as these liposomes specifically home to the tumor vascular endothelium. Therefore, a polyethylene glycol (PEG)-grafted cationic liposomal formulation containing the photosensitizer zinc phthalocyanine was developed. The formulation was optimized with respect to photodynamic activity and cellular uptake, and the intracellular localization of the photosensitizer and the main modes of cell death induced by PDT were determined. Lastly, systemic toxicity profiles were established in mice. This study demonstrated that a PEGylated cationic liposomes containing zinc phthalocyanine were effective in vitro and was well-tolerated in vivo. Further ongoing investigations will focus on obtaining in vivo proof-ofconcept regarding drug delivery and PDT efficacy.