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Photodynamic therapy (PDT) is a minimally invasive treatment that uses the combination of a photosensitizing agent (PS) and light to selectively target solid tumors, as well as several non-neoplastic proliferating cell diseases. After systemic administration, PSs are activated by localized irradiation with visible light; in the presence of adequate concentrations of molecular oxygen, this causes the formation of reactive oxygen species (ROS) and subsequent tissue damage. In this study, two series of tetrakis( N -alkylpyridinium-4-yl)porphyrins were synthesized, differing in the presence or absence of a zinc ion in the tetrapyrrole nucleus, as well as in the N -alkyl chain length (from one to twelve carbon atoms). The compounds were chemically characterized, and their effect on cell viability was evaluated using a panel of three tumor cell lines to determine a possible relationship between photodynamic activity and Zn presence/alkyl chain length. The types of cell death mechanisms involved in the effect of the various PSs were also evaluated. The obtained results indicate that the most effective porphyrin is the Zn-porphyrin, with a pendant made up of eight carbon atoms ( Zn-C8 ).

In photodynamic therapy (PDT), a photosensitizer (PS) excited with a specific wavelength, and in the presence of oxygen, gives rise to photochemical reactions that lead to cell damage. Over the past few years, larval stages of the G. mellonella moth have proven to be an excellent alternative animal model for in vivo toxicity testing of novel compounds and virulence testing. In this article, we report a series of preliminary studies on G. mellonella larvae to evaluate the photoinduced stress response by a porphyrin (PS) (TPPOH). The tests performed evaluated PS toxicity on larvae and cytotoxicity on hemocytes, both in dark conditions and following PDT. Cellular uptake was also evaluated by fluorescence and flow cytometry. The results obtained demonstrate how the administration of PS and subsequent irradiation of larvae affects not only larvae survival rate, but also immune system cells. It was also possible to verify PS's uptake and uptake kinetics in hemocytes, observing a maximum peak at 8 h. Given the results obtained in these preliminary tests, G. mellonella appears to be a promising model for preclinical PS tests.

The visible light combined with photosensitizers (PSs) is exploited in both antitumoral and antimicrobial fields inducing a photo-oxidative stress within the target cells. Among the different PSs, porphyrins belong to the family of the most promising compounds to be used in clinical photodynamic applications. Although in the last years many porphyrins have been synthesised and tested, only a few reports concern the in vitro effects of the 5,15-diarylporphyrins. In this work, the activity of four 5,15-diarylporphyrins (compounds 7-10), bearing alkoxy-linked pyridinium appendixes, have been tested on cancer cell lines and against bacterial cultures. Among the synthetized PSs, compounds 7 and 9 are not symmetrically substituted porphyrins showing one cationic charge tethered at the end of one 4C or 8C carbon chains, respectively. On the other hand, compounds 8 and 10 are symmetrically substituted and show two chains of C4 and C8 carbons featuring a cationic charge at the end of both chains. The dicationic 8 and 10 were more hydrophilic than monocationic 7 and 9, outlining that the presence of two pyridinium salts have a higher impact on the solubility in the aqueous phase than the lipophilic effect exerted by the length of the alkyl chains. Furthermore, these four PSs showed a similar rate of photobleaching, irrespective of the length and number of chains and the number of positive charges. Among the eukaryotic cell lines, the SKOV3 cells were particularly sensitive to the photodynamic activity of all the tested diarylporphyrins, while the HCT116 cells were found more sensitive to PSs bearing C4 chain (7 and 8), regardless the number of cationic charges. The photo-induced killing effect of these porphyrins was also tested against two different bacterial cultures. As expected, the Gram positive Bacillus subtilis was more sensitive than the Gram negative Escherichia coli, and the dicationic porphyrin 8, bearing two C4 chains, was the most efficient on both microorganisms. In conclusion, the new compound 8 seems to be an optimal candidate to deepen as versatile anticancer and antibacterial photosensitizer., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Photodynamic therapy (PDT) of cancer uses photosensitizers (PS), a light source and oxygen to generate high levels of reactive oxygen species (ROS), that exert a cytotoxic action on tumor cells. Recently, it has been shown that mixed non-symmetrical diaryl porphyrins, with two different pendants, are more photodynamically active than symmetrical diaryl porphyrins. In the present study, we investigate the in vitro photodynamic effects of four novel non-symmetrical diaryl porphyrins, two of which bear one pentafluoro-phenyl and one bromo-alkyl (apolar) pendant, whereas the two others bear one pentafluoro-phenyl and one cationic pyridine pendant. The four compounds were tested in a small panel of human cancer cell lines, and their photodynamic activities were compared with that of m-THPC (Foscan), currently the most successful PS approved for clinical use in cancer PDT. The results of the cytotoxicity studies indicate that the two molecules bearing the cationic pendant are more potent in vitro than those with the apolar pendant, and that they are as potent as Foscan. To gain further insights into the mechanism of PS-induced phototoxicity, induction of apoptotic, autophagic and necrotic cell death, and generation of reactive oxygen species (ROS) were evaluated in cancer cells following exposure to the PSs and irradiation. The effect of the PSs on the migratory activity of the cells was also assessed. The data obtained from this work support a greater potency of diaryl porphyrins with a positive charge in inducing cell death, as compared to those with the bromo-alkyl pendant; most importantly, some of these novel compounds exhibit features that might make them superior to the clinically approved PS Foscan., (Copyright © 2019 Elsevier B.V. All rights reserved.)