Far-Red-Absorbing Cationic Phthalocyanine Photosensitizers: Synthesis and Evaluation of the Photodynamic Anticancer Activity and the Mode of Cell Death Induction

Novel zinc, magnesium, and metal-free
octasubstituted phthalocyanine
photosensitizers bearing [(triethylammonio)­ethyl]­sulfanyl substituents
in the peripheral or nonperipheral positions were synthesized and
investigated for their photophysical properties (ΦΔ value up to 0.91, λmax up to 750 nm) and photodynamic
anticancer activity. The photodynamic treatment of 3T3, HeLa, SK-MEL-28,
and HCT 116 cancer cells revealed that the magnesium complexes were
not active (IC50 > 100 μM), whereas the IC50 values of the zinc complexes typically reached values in
the submicromolar
range with low toxicity in the dark (TC50 ≈ 1500
μM). The subcellular changes upon photodynamic treatment of
the HeLa cells indicated that the studied photosensitizers induced
damage primarily to the lysosomes, which was followed by a relocalization
and damage to other organelles. The time-lapse morphological changes
along with the flow cytometry and caspase activity measurements indicated
a predominant involvement of necrosis-like cell death.