Amphiphilic zinc phthalocyanine photosensitizers: synthesis, photophysicochemical properties and in vitro studies for photodynamic therapy

Abstract

Peripherally and non-peripherally tetra-substituted zinc(ii) phthalocyanines bearing 2-(2-{2-[3-(dimethylamino)phenoxy]ethoxy}ethoxy)ethoxy and 2-(2-{2-[3-(diethylamino)phenoxy]ethoxy}ethoxy)ethoxy groups (, , and ) were synthesized by cyclotetramerization of the corresponding phthalonitriles (, , and ). Their quaternized ionic derivatives (, , and ) were also synthesized by the reaction of them with methyl iodide. The novel compounds were characterized by using standard spectroscopic techniques such as FT-IR, (1)H NMR, (13)C NMR, UV-vis, mass and elemental analyses. The obtained quaternized phthalocyanines (, , and ) showed amphiphilic behaviour with excellent solubility in both organic and aqueous solutions, which makes them potential photosensitizers for use in photodynamic therapy (PDT) of cancer. The photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen and photodegradation quantum yields) properties of these novel phthalocyanines were studied in DMSO for both non-ionic and ionic quaternized derivatives. However, these properties were examined in both DMSO and phosphate buffer solution (PBS) for quaternized ionic phthalocyanines. The effects of the positions of substituents (peripheral or non-peripheral) and the quaternization of the nitrogen atoms on the substituents about their photophysical and photochemical properties were also compared in this study. The bovine serum albumin (BSA) binding behaviours of the studied quaternized ionic zinc(ii) phthalocyanines were also described in PBS solutions. The quaternized phthalocyanines (, , and ) successfully displayed light-dependent photodamage in HeLa and HuH-7 cancer cells in photodynamic therapy treatment. The photosensitivity and the intensity of damage were found directly related to the concentration of the photosensitizers.

Unveiling Ga(III) phthalocyanine—a different photosensitizer in neuroblastoma cellular model

“…Owing to their excellent solubility in both organic and aqueous solutions, they are potential PS for use in PDT of cancer . The photophysical (fluorescence quantum yields and life‐times) and photochemical (singlet oxygen and photodegradation quantum yields) properties of these novel Pcs were exploited in light‐dependent photodamage in HeLa, HuH‐7, and K562 cancer cells . Using an established improved toxicological testing workflow, we found that the photosensitivity and the intensity of damage are directly related to the concentration of the PS.…”

Metal ion sensing soluble α or β tetrasubstituted gallium and indium phthalocyanines: Synthesis, characterization, photochemistry and aggregation behaviors

“…I abs and I Std abs are the rates of light absorption by the samples (3, 4, 5 and 6) and standard, respectively. To avoid chain reactions induced by DPBF in the presence of singlet oxygen [35], the concentration of quencher (DPBF) was lowered to $3 Â 10 À5 mol dm À3 Solutions of sensitizer (containing DPBF) were prepared in the dark and irradiated in the Q band region using the setup described above. DPBF degradation at 417 nm (in DMSO) were monitored.…”

“…Thus, Photodegradation quantum yield (U d ) determinations were carried out by the experimental set-up described in literature [35][36][37]. Photodegradation quantum yields were determined using formula (3),…”

Synthesis and Encapsulation of a New Zinc Phthalocyanine Photosensitizer into Polymeric Nanoparticles to Enhance Cell Uptake and Phototoxicity

“…In one study, ZnPc was encapsulated into poly(lactic-co-glycolic acid) (PLGA) nanoparticles having a diameter size of 227 to 450 nm utilizing the emulsion evaporation method [12]. Another research group attempted to encapsulate ZnPc into polycaprolactone (PCL) using a solvent emulsification-evaporation method to obtain nanoparticles with a diameter size of 187 nm [13]. However, neither of these previous studies reported on the cellular uptake of the particles obtained nor on the resultant cytotoxicity of the encapsulated dye.…”

“…Hydrophobic PSs also tend to remain longer in the patient's body compared to hydrophilic PSs. These observations have caused PSs with amphiphilic properties through conjugation with water-soluble or amphiphilic polymers to become attractive in PDT studies [6,[13][14][15][16][17].…”