Effect of fluorinated substituents of Zn phthalocyanine: nanoencapsulation and phototoxicity

Phthalocyanines are promising photosensitizers for photodynamic therapy due to their advantageous light absorption properties and low dark toxicity. Two non-peripheral substituted phthalocyanines, tetra-ethoxy-Zn-phthalocyanine (CH₃Pc) and its fluorinated analogue (CF₃Pc), were combined with different nanocarriers, and their photophysical properties and biological activities were studied. Carrier-encapsulation and phthalocyanines' aggregation state were probed by NMR-, UV-Vis-, and fluorescence spectroscopy. Five different carrier systems were compared: polyvinylpyrrolidone (PVP), two triblock copolymer micelles (Synperonic P84, "P84", and Pluronic F127, "F127"), self-emulsifying detergent micelles (Kolliphor RH40, "RH40"), and 1, 2-dioleoyl-sn-glycero-3-phosphocholine unilamellar vesicles (ULVs). CH₃Pc inserted efficiently into P84, F127 and RH40 micelles in monomeric form, while CF₃Pc was encapsulated as dimers and oligomers. ULVs were capable to efficiently monomerize and encapsulate both phthalocyanines. PVP was not suitable to solubilize neither of these phthalocyanines. The localization of CH₃Pc and CF₃Pc at the carrier interfaces was determined by NMR-experiments with atomic resolution. All phthalocyanine-carrier systems - except PVP - exhibited efficient singlet oxygen production, with ULVs reaching the highest quantum yields. The photodynamic potential of the different CH₃Pc- and CF₃Pc-formulations was studied using a human breast cancer cell line (MCF-7) by measuring the dark toxicity and phototoxicity after light irradiation at 655 nm. Encapsulation into ULVs and RH40 micelles exhibited the highest photodynamic efficiency for both phthalocyanines at low concentrations (0.05-1 µM). The fluorinated phthalocyanine showed enhanced photodynamic activity compared to its non-fluorinated analogue. While micellar carriers easily monomerized CH₃Pc, ULV-encapsulated CF₃Pc turned out to be the best candidate as efficient sensitizer for photodynamic therapy.