Effect of fluorinated substituents of Zn phthalocyanine: nanoencapsulation and phototoxicity

• The effect of fluorinated substituents on phthalocyanines’ PDT potential was investigated. • Carrier type strongly affects aggregation, 1 O 2 yield, and PDT efficiency of CH 3 Pc and CF 3 Pc. • CF 3 Pc had greater PDT efficacy than its non-fluorinated analogue. • Unilamellar vesicle-encapsulated CF 3 Pc emerged as the most promising PDT candidate • NMR provided detailed information on the drug localization at the carrier interface. 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 ( CH 3 Pc ) and its fluorinated analogue ( CF 3 Pc ), 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 ( ULV s). CH 3 Pc inserted efficiently into P84 , F127 and RH40 micelles in monomeric form, while CF 3 Pc was encapsulated as dimers and oligomers. ULV s were capable to efficiently monomerize and encapsulate both phthalocyanines. PVP was not suitable to solubilize neither of these phthalocyanines. The localization of CH 3 Pc and CF 3 Pc at the carrier interfaces was determined by NMR-experiments with atomic resolution. All phthalocyanine-carrier systems − except PVP − exhibited efficient singlet oxygen production, with ULV s reaching the highest quantum yields. The photodynamic potential of the different CH 3 Pc - and CF 3 Pc -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 ULV s 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 CH 3 Pc , ULV -encapsulated CF 3 Pc turned out to be the best candidate as efficient sensitizer for photodynamic therapy.