Tetra(3,4-pyrido)porphyrazines Caught in the Cationic Cage: Toward Nanomolar Active Photosensitizers

Abstract

Investigation of a series of tetra(3,4-pyrido)porphyrazines (TPyPzs) substituted with hydrophilic substituents revealed important structure-activity relationships for their use in photodynamic therapy (PDT). Among them, a cationic TPyPz derivative with total of 12 cationic charges above, below and in the plane of the core featured a unique spatial arrangement that caught the hydrophobic core in a cage, thereby protecting it fully from aggregation in water. This derivative exhibited exceptionally effective photodynamic activity on a number of tumor cell lines (HeLa, SK-MEL-28, A549, MCF-7) with effective concentrations (EC) typically below 5 nM, at least an order of magnitude better than the EC values obtained for the clinically approved photosensitizers verteporfin, temoporfin, protoporphyrin IX, and trisulfonated hydroxyaluminum phthalocyanine. Its very low dark toxicity (TC > 400 μM) and high ability to induce photodamage to endothelial cells (EA.hy926) without preincubation suggest the high potential of this cationic TPyPz derivative in vascular-targeted PDT.

31P NMR Evidence for Peroxide Intermediates in Lipid Emulsion Photooxidations: Phosphine Substituent Effects in Trapping

“…At 90 J cm −2 , the percent yield of 2 oxide decreased from 9.3% to 5% with decreasing AlPcS concentration from 100 μ m to 10 n m . Photoactivity of sensitizers in nanomolar quantities is of interest in the field of PDT , and while our data show 5% photooxidation at 10 n m concentrations of AlPcS, effects such as the location of the sensitizer in Intralipid were not assessed.…”

Binding of an amphiphilic phthalocyanine to pre-formed liposomes confers light-triggered cargo release

“…The studied PS were prepared by either recently published procedures (for water-soluble non-aggregating cationic azaphthalocyanine 1 ) 43 or via a novel synthetic approach for unsymmetrical, amphiphilic phthalocyanine 2 (Fig 1). This compound was designed to contain flat hydrophobic phthalocyanine core that could easily insert into the lipid bilayer.…”

“…Compound 1 is a polycationic tetra(3,4-pyrido)porphyrazine and is highly water soluble with practically no distribution to lipophilic phases 43 . Phthalocyanine 2 is sparingly water soluble, producing a weakly green saturated water solution but it dissolves well in DMSO and DMF.…”

“…Phthalocyanine 2 is sparingly water soluble, producing a weakly green saturated water solution but it dissolves well in DMSO and DMF. The amphiphilic nature of 2 suggests that in water-based media it would likely form dimers or aggregates with low fluorescence and singlet oxygen generating properties 43 . To test this hypothesis UV−vis spectroscopy was used to assess the absorption spectra of 1 and 2 dissolved in different media: de-ionized water, dPBS, a surfactant (0.25% Triton X-100), and a liposomal solution.…”

“…The instrument was calibrated externally with a five-point calibration using a Peptide Calibration Mix1 kit (LaserBio Laboratories, Sophia- Antipolis, France). Compounds 1 43 and 3 44 were prepared by published methods.…”