Properties of halogenated and sulfonated porphyrins relevant for the selection of photosensitizers in anticancer and antimicrobial therapies

Abstract

The impact of substituents on the photochemical and biological properties of tetraphenylporphyrin-based photosensitizers for photodynamic therapy of cancer (PDT) as well as photodynamic inactivation of microorganisms (PDI) was examined. Spectroscopic and physicochemical properties were related with therapeutic efficacy in PDT of cancer and PDI of microbial cells in vitro. Less polar halogenated, sulfonamide porphyrins were most readily taken up by cells compared to hydrophilic and anionic porphyrins. The uptake and PDT of a hydrophilic porphyrin was significantly enhanced with incorporation in polymeric micelles (Pluronic L121). Photodynamic inactivation studies were performed against Gram-positive (S. aureus, E. faecalis), Gram-negative bacteria (E. coli, P. aeruginosa, S. marcescens) and fungal yeast (C. albicans). We observed a 6 logs reduction of S. aureus after irradiation (10 J/cm2) in the presence of 20 μM of hydrophilic porphyrin, but this was not improved with incorporation in Pluronic L121. A 2–3 logs reduction was obtained for E. coli using similar doses, and a decrease of 3–4 logs was achieved for C. albicans. Rational substitution of tetraphenylporphyrins improves their photodynamic properties and informs on strategies to obtain photosensitizers for efficient PDT and PDI. However, the design of the photosensitizers must be accompanied by the development of tailored drug formulations.

Enhanced Cellular Uptake and Photodynamic Effect with Amphiphilic Fluorinated Porphyrins: The Role of Sulfoester Groups and the Nature of Reactive Oxygen Species

“…40% at the same concentration. Similar results were also obtained for sulfonamide analogs [30,31]. For comparison, sulfonate porphyrins showed cytotoxicity at 100 µM concentrations [29].…”

“…However, according to our previous data published for sulfonic derivative (F 2 POH), some of them (especially difluorinated ones) are characterized by a more intense Q x band, which is further displaced to the red region of spectra (close to 650 nm). Considering that F 2 POH was shown to be efficient photosensitizer in vitro in both anticancer photodynamic effect as well as antimicrobial photoinactivation [31], it can be expected that the sulfonate ester substituents studied in this work may increase the phototoxicity of these photosensitizers.…”

“…Some of us reported the fundamental spectroscopic and photophysical properties of investigated photosensitizers determined in ethanol [31,38]. The ground state absorption and fluorescence spectra of sulfonate ester porphyrin derivatives, recorded at room temperature in DMSO, are presented in Figure 1.…”

“…UV/VIS/NIR electronic absorption spectra were recorded in quartz cuvettes (l = 1 cm) using Shimadzu 2100 spectrophotometer (Shimadzu Corp., Kioto, Japan). Fluorescence emission spectra were recorded from 550 nm to 750 nm with excitation at the Soret band (420 nm) using a Fluorescence Spectrometer LS 55 (Perkin Elmer, Cracow, Poland) [31].…”

“…Subsequently, it was demonstrated that bacteriochlorins (e.g. sulfonamide derivatives bearing Cl or F substituents in the ortho positions of the phenyl rings) have even better properties for PDT, including strong absorption in the near-infrared (λ max ≈ 750 nm, ε ≈ 10 5 M −1 cm −1 ), excellent cellular uptake, intracellular localization, low cytotoxicity in the dark, and high phototoxicity upon irradiation with red light [6,28,[30][31][32][33]. These and other bacteriochlorin-based photosensitizers proved to be very efficient in vascular-targeted PDT [34,35].…”