Tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine for photodynamic cancer therapy

• We propose new promising photosensitizer (ZnPc) for photodynamic cancer therapy.
• Photoactivated ZnPc dose-dependently decreased cancer cell growth by almost 100%.
• Photoactivated ZnPc caused cancer cells death via apoptosis and cell cycle arrest.
• ZnPc exhibited antiangiogenic potency, as evaluated by in vivo experiments.
• Non-photoactivated ZnPc did not show any cytotoxic effects (“dark toxicity”).

Photodynamic therapy (PDT) has emerged as an effective and minimally invasive treatment option for several diseases, including some forms of cancer. However, several drawbacks of the approved photosensitizers (PS), such as insufficient light absorption at therapeutically relevant wavelengths hampered the clinical effectiveness of PDT. Phthalocyanines (Pc) are interesting PS-candidates with a strong light absorption in the favourable red spectral region and a high quantum yield of cancer cell destroying singlet oxygen generation. Here, we evaluated the suitability of tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) as novel PS for PDT.ZnPc-induced phototoxicity, induction of apoptosis as well as cell cycle arresting effects was studied in the human gastrointestinal cancer cell lines of different origin. Photoactivation of ZnPc-pretreated (1–10 μM) cancer cells was achieved by illumination with a broad band white light source (400–700 nm) at a power density of 10 J/cm2.Photoactivation of ZnPc-loaded cells revealed strong phototoxic effects, leading to a dose-dependent decrease of cancer cell proliferation of up to almost 100%, the induction of apoptosis and a G1-phase arrest of the cell cycle, which was associated with decrease in cyclin D1 expression. By contrast, ZnPc-treatment without illumination did not induce any cytotoxicity, apoptosis, cell cycle arrest or decreased cell growth. Antiangiogenic effects of ZnPc-PDT were investigated in vivo by performing CAM assays, which revealed a marked degradation of blood vessels and the capillary plexus of the chorioallantoic membrane of fertilized chicken eggs. Based on our data we think that ZnPc may be a promising novel photosensitizer for innovative PDT.