Photodynamic therapy (
PDT) is a
cancer treatment involving systemic administration of a
tumor-localizing
photosensitizer; this, when activated by the appropriate wavelength of light, interacts with molecular
oxygen to form a toxic, short-lived species known as
singlet oxygen, which is thought to mediate cellular death.
Photofrin, a
complex mixture of
porphyrin oligomers has recently received FDA approval for the photodynamic treatment of esophageal and endobronchial
carcinoma, but its photodynamic and toxicity profiles are far from ideal. In the present study we evaluated a series of
porphyrin-based PSs, some of which newly synthesized by our group, with the aim to identify agents with more favorable characteristics. For the most effective compounds in the
porphyrin series,
chlorin analogs were also synthesized; for comparison, the screening also included
Photofrin. Cytotoxicity studies were performed by the MTT assay on a cultured human
colon adenocarcinoma cell line (HCT116); the results indicate that the 3,4,5-trimethoxyphenyl, 3OH- and 4OH-phenyl, and the sulfonamidophenyl derivatives are significantly more potent than
Photofrin. Flow cytometric studies and fluorescence microscopy indicate that in
PDT-treated HCT116 cells death occurs mainly by apoptosis. In summary, novel PSs described in the present study, belonging both to the
porphyrin and
chlorin series, have proven more effective than
Photofrin in killing
colon cancer cells in vitro; extending these observation to in vivo models, particularly regarding the deeper reaching
chlorin derivatives, might lead to significant advances in the development of
tumor PDT.