Photooxidation and Phototoxicity of pi-extended squaraines.
This paper describes the synthesis of pi-extended squaraines and their photooxidation properties and gives an in-depth characterization of these molecules as photosensitizing agents. Squaraines show a strong absorption in the tissue transparency window (600-800 nm), and upon irradiation, they undergo a photooxidation process, leading to the formation of peroxide and hydroperoxide radicals according to a type I radical chain process. Confocal laser microscopy demonstrates that the designed squaraines efficiently internalize in the cytoplasm and not in the nucleus of the cell. In the dark, they are scarcely cytotoxic, but after irradition, they promote a strong dose-dependent phototoxic effect in four different cancer cells. In HeLa and MCF-7 cells, squaraines 4 and 5, thanks to their hydrocarbon tails, associate to the membranes and induce lipid peroxidation, as indicated by a marked increase of malonyldialdehyde after photodynamic treatment, in agreement with in vitro photooxidation studies. FACS, caspase-3/7 assays and time-lapse microscopy demonstrate that the designed squaraines cause cell death primarily by necrosis.
Rapozzi
Valentina
V
Department of Biomedical Science and Technology, University of Udine, Ple Kolbe 4, I-33100 Udine, Italy.
Beverina
Luca
L
Salice
Patrizio
P
Pagani
Giorgio A
GA
Camerin
Monica
M
Xodo
Luigi E
LE
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003503:Cyclobutanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017484:Dermatitis, Phototoxic / Q000378:metabolism*; D005434:Flow Cytometry; D008401:Gas Chromatography-Mass Spectrometry; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008054:Lipid Peroxides / Q000378:metabolism*; D018613:Microscopy, Confocal; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D000970:Antineoplastic Agents; D052160:Benzothiazoles; D003503:Cyclobutanes; D008054:Lipid Peroxides; D017319:Photosensitizing Agents; D017392:Thiobarbituric Acid Reactive Substances