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Antimicrobial photodynamic therapy (aPDT) is gaining a special importance as an effective approach against multidrug-resistant strains responsible of fatal infections. The addition of potassium iodide (KI), a non-toxic salt, is recognized to increase the aPDT efficiency of some photosensitizers (PSs) on a broad-spectrum of microorganisms. As the reported cases only refer positive aPDT potentiation results, in this work we selected a broad range of porphyrinic and non-porphyrinic PSs in order to gain a more comprehensive knowledge about this aPDT potentiation by KI. For this evaluation were selected a series of meso-tetraarylporphyrins positively charged at meso positions or at β-pyrrolic positions and the non-porphyrinic dyes Methylene blue, Rose Bengal, Toluidine Blue O, Malachite Green and Crystal Violet; the assays were performed using a bioluminescent E. coli strain as a model. The results indicate that KI has also the ability to potentiate the aPDT process mediated by some of the cationic PSs [Tri-Py(+)-Me, Tetra-Py(+)-Me, Form, RB, MB, Mono-Py(+)-Me, β-ImiPhTPP, β-ImiPyTPP, and β-BrImiPyTPP] allowing a drastic reduction of the treatment time as well as of the PS concentration. However, the efficacy of some porphyrinic and non-porphyrinic PSs [Di-Py(+)-Me opp, Di-Py(+)-Me adj, Tetra-Py, TBO, CV, and MG] was not improved by the presence of the coadjuvant. For the PSs tested in this study, the ones capable to decompose the peroxyiodide into iodine (easily detectable by spectroscopy or by the visual appearance of a blue color in the presence of amylose) were the most promising ones to be used in combination with KI. Although these studies confirmed that the generation of 1O2 is an important fact in this process, the PS structure (charge number and charge position), aggregation behavior and affinity for the cell membrane are also important features to be taken in account.

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In this highlight an overview of the advances performed by the Aveiro group on the design and synthesis of tetrapyrrolic photosensitizers with potential photodynamic antimicrobial activity is presented.

Studies on the synthesis, preliminary in vivo biological activity, singlet oxygen and fluorescence yields of a dimeric porphyrin (D1) are described. The pharmacokinetic behavior and photodynamic properties of the dimer D1 were examined in Balb/c mice bearing an MS-2 fibrosarcoma. Compound D1 shows a high selectivity for tumor localization (tumor/peritumoral tissue ratios of dye concentration ranging between ca 100 and 140 at 24 h after drug administration of 5.0-1.0 mg kg-1 into DL-alpha-dipalmitoylphosphatidylcholine liposomes). The phototherapeutic efficiency of dimer D1 was evaluated by following the growth curves of fibrosarcoma irradiated with red light (600-700 nm) with a total dose of 400 J cm-2, at 24 h after intravenous injection. Photodynamic therapy-treated tumors showed a significant delay in growth as compared to untreated control mice. The results obtained suggest that the porphyrin dimer D1 may be a promising candidate for further use in PDT experiments.