Amphiphilic Cationic Phthalocyanines for Photodynamic Therapy of Cancer

Effective interaction with biomembranes is essential for activity of photosensitizers; however, majority of them are highly charged symmetrical species. Amphiphilic cationic phthalocyanines differing in bulkiness of substitution on lipophilic part (-H, -SMe, -StBu) were therefore prepared. Compounds had high singlet oxygen production (Φ_Δ =0.38-0.46, DMSO), good fluorescence emission (Φ_F =0.21-0.26, DMSO), and log P values ranging -0.07-1.1 (1-octanol/PBS). Study of interaction with liposomes revealed that also bulky -StBu derivatives are able to enter biomembranes. Detail in vitro studies (toxicity, subcellular localization, type of cell death, and morphology) were performed. Compounds were characterized by excellent EC₅₀ values in range of dozens of nM (HeLa, EA.hy926, MCF-7, HCT116), which were dependent on drug-light interval and reached plateau after 4 h on HeLa cells. Well-balanced lipophilicity with ability to interact with biomembranes rank these derivatives among perspective photosensitizers, even for vascular-targeted PDT (VTP) since they kill EA.hy926 without any preincubation time.