Fluorination of phthalocyanine substituents: Improved photoproperties and enhanced photodynamic efficacy after optimal micellar formulations.
A fluorinated phthalocyanine and its non-fluorinated analogue were selected to evaluate the potential enhancement of fluorination on photophysical, photochemical and redox properties as well as on biological activity in cellular and animal models. Due to the pharmacological relevance, the affinity of these phthalocyanines towards biological membranes (logPow) as well as their primary interaction with human serum albumin (HSA) or low-density lipoprotein (LDL) were determined. Water-dispersible drug formulation of phthalocyanines via Pluronic®-based triblock copolymer micelles was prepared to avoid self-aggregation effects and to improve their delivery. The obtained results demonstrate that phthalocyanines incorporation into tunable-polymeric micelles significantly enhanced their cellular uptake and their photocytotoxicity. The improved biodistribution and photodynamic efficacy of the phthalocyanines-triblock copolymer conjugates was also confirmed in vivo in CT26 bearing BALB/c mice. PDT with both compounds led to tumor growth inhibition in all treated animals. Fluorinated phthalocyanine 2 turned out to be the most effective anticancer agent as the tumors of 20% of mice treated regressed completely and did not appear for over one year after treatment.
Faculty of Chemistry, Jagiellonian University, 30-060 Kraków, Poland.
Barbara
B
Pucelik
TÜBITAK Marmara Research Center, Materials Institute, P.O. Box 21, 41470 Gebze, Kocaeli, Turkey.
Ilke
I
Gürol
Gebze Technical University, Department of Chemistry, P.O. Box 141, 41400 Gebze, Kocaeli, Turkey.
Vefa
V
Ahsen
Gebze Technical University, Department of Chemistry, P.O. Box 141, 41400 Gebze, Kocaeli, Turkey. Electronic address: fdumoulin@gtu.edu.tr.
Fabienne
F
Dumoulin
Faculty of Chemistry, Jagiellonian University, 30-060 Kraków, Poland. Electronic address: jdabrows@chemia.uj.edu.pl.
Janusz M
JM
Dąbrowski
D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D004339:Drug Compounding; D004355:Drug Stability; D054879:Halogenation; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D054833:Isoindoles; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D051379:Mice; D008823:Micelles; D008875:Middle Aged; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D012709:Serum Albumin / Q000378:metabolism; D026082:Singlet Oxygen / Q000378:metabolism; D014018:Tissue Distribution
D007211:Indoles; D054833:Isoindoles; D008077:Lipoproteins, LDL; D008823:Micelles; D017319:Photosensitizing Agents; D012709:Serum Albumin; D026082:Singlet Oxygen; C013647:phthalocyanine
Anticancer activity; Biodistribution; Cancer; Fluorination; Photodynamic therapy; Phthalocyanines; Reactive oxygen species (ROS)