Abstract
Photodynamic
therapy is a treatment modality of cancer based on
the production of cytotoxic species upon the light activation of photosensitizers.
Zinc phthalocyanine photosensitizers bearing four or eight bulky 2,6-di(pyridin-3-yl)phenoxy
substituents were synthesized, and pyridyl moieties were methylated.
The quaternized derivatives did not aggregate at all in water and
retained their good photophysical properties. High photodynamic activity
of these phthalocyanines was demonstrated on HeLa, MCF-7, and EA.hy926
cells with a very low EC
50
of 50 nM (for the MCF-7 cell
line) upon light activation while maintaining low toxicity in the
dark (TC
50
≈ 600 μM), giving thus good phototherapeutic
indexes (TC
50
/EC
50
) above 1400. The compounds
localized primarily in the lysosomes, leading to their rupture after
light activation. This induced an apoptotic cell death pathway with
secondary necrosis because of extensive and swift damage to the cells.
This work demonstrates the importance of a bulky and rigid arrangement
of peripheral substituents in the development of photosensitizers.