engleski

In vitro photodynamic activity of a new tri- cationic amphiphilic porphyrin against herpes simplex virus 1, bacteria and cancer cells

Photodynamic therapy (PDT) is a type of phototherapy that uses harmless red light for the activation of a photosensitiser (PS) and consequential, localised formation of the cytotoxic singlet oxygen or other reactive oxygen species.1Even though PDT was first discovered on a microorganism, it has been primarily developed to treat cancer, and is only recently getting more attention as an antimicrobial therapy.2 We have synthesized 5-(4- octadecanamidophenyl)-10, 15, 20-tris(N- methylpyridinium-3-yl)porphyrin trichloride (C18PyP3) in order to investigate the effect of the lipophilic moiety on PDT activity of this amphiphilic porphyrin, in comparison to the hydrophilic analogue, 5-(4- acetamidophenyl)-10, 15, 20- tris(N-methylpyridinium-3-yl)porphyrin trichloride (C2PyP3). Both porphyrins have very similar optical properties and PDT activity in relation to both drug-dose and light-dose, but significantly higher activity of the amphiphilic porphyrin was demonstrated as the obtained IC50 value for C18PyP3 was 37 times lower than for C2PyP3, after PS activation with low dose of red light (1.8 J cm-2, 643 nm) on HeLa cells in vitro. 3 Cationic tetraarylporphyrins have been previously used to destroy both Gram positive and Gram negative bacteria, 4 and are also interesting as possible antiviral agents.5 To test the antibacterial activity of C18PyP3, the minimum inhibitory (MIC) and minimum bactericidal (MBC) concentration was determined, with the dilution method, on several Gram (+) and Gram (-) bacteria. After 30 minutes incubation with C18PyP3 and further 1 hour of irradiation (overall dose 7.2 J cm-2), there was no difference between MIC and MBC values, and the lowest values were obtained on Gram (+) bacteria, namely, Staphylococcus aureus (6.25 µM), including methicillin-resistant strain (MRSA), Enterococcus faecalis (12.5 µM) and Listeria monocytogenes (12.5 µM). Finally, to test antiviral activity of C18PyP3, we infected Vero cells treated with different concentrations of the compound with herpes simplex virus 1 (HSV-1) and measured virus yield. Replication of the virus was greatly reduced in cells that were treated and irradiated (1.8 J cm-2) compared to untreated or treated but not irradiated cells. Moreover, the inhibition of replication was drug-dose dependent. These results strongly indicate that C18PyP3 activated by light exerts antiviral properties. Furthermore, our preliminary results show that it affects HSV-1 replication by inhibiting virus gene expression and by limiting the infectivity of HSV-1 virions. Important to note, the concentrations of C18PyP3 used in these experiments did not show a significant toxicity in Vero cells.

Porphyrin ; Photodynamic therapy ; Cancer ; Bacteria ; Herpes simplex virus 1

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