Fluorination of phthalocyanine substituents: Improved photoproperties and enhanced photodynamic efficacy after optimal micellar formulations

Pucelik B., Gurol I., Ahsen V., DUMOULIN F., Dabrowski J. M.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, cilt.124, ss.284-298, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 124
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1016/j.ejmech.2016.08.035
  • Dergi Adı: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.284-298
  • Anahtar Kelimeler: Anticancer activity, Biodistribution, Cancer, Fluorination, Photodynamic therapy, Phthalocyanines, Reactive oxygen species (ROS), BLOCK-COPOLYMER MICELLES, SINGLET-OXYGEN, POLYACRYLAMIDE NANOPARTICLES, BENZOPORPHYRIN DERIVATIVES, SPECTROSCOPIC PROPERTIES, ANTICANCER ACTIVITY, PLURONIC F127, THERAPY, DRUG, BACTERIOCHLORIN
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Hayır

Özet

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 (logP(ow)) 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 (R)-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. (C) 2016 Elsevier Masson SAS. All rights reserved.