Antimicrobial photodynamic therapy (APDT) has received a great deal of attention due to its unique ability to kill all currently known classes of microorganisms. To date, infectious diseases caused by bacteria and viruses are one of the main sources of high mortality, mass epidemics and global pandemics among humans. Every year, the emergence of three to four previously unknown species of viruses dangerous to humans is recorded, totaling more than 2/3 of all newly discovered human pathogens. The emergence of bacteria with multidrug resistance leads to the rapid obsolescence of antibiotics and the need to create new types of antibiotics. From this point of view, photodynamic inactivation of viruses and bacteria is of particular interest. This review summarizes the most relevant mechanisms of antiviral and antibacterial action of APDT, molecular targets and correlation between the structure of cationic porphyrins and their photodynamic activity.
Photodynamic therapy (PDT) in oncology is characterized by low invasiveness, minimal side effects, and little tissue scarring. Increasing the selectivity of PDT agents toward a cellular target is a new approach intended to improve this method. This study is devoted to the design and synthesis of a new conjugate based on meso-arylporphyrin with a low-molecular-weight tyrosine kinase inhibitor, Erlotinib. A nano-formulation based on Pluronic F127 micelles was obtained and characterized. The photophysical and photochemical properties and biological activity of the studied compounds and their nano-formulation were studied. A significant, 20–40-fold difference between the dark and photoinduced activity was achieved for the conjugate nanomicelles. After irradiation, the studied conjugate nanomicelles were 1.8 times more toxic toward the EGFR-overexpressing cell line MDA-MB-231 compared to the conditionally normal NKE cells. The IC50 was 0.073 ± 0.014 μM for the MDA-MB-231 cell line and 0.13 ± 0.018 μM for NKE cells after irradiation for the target conjugate nanomicelles.
This paper reports on the design and synthesis of new multifunctional porphyrin-based therapeutic agents for potential therapeutic and diagnostic applications. Zinc complexes of A3B-type meso-arylporphyrins containing OH- and COOH- groups were modified with chelating ligands based on 4′-(4-methylphenyl)-2,2′:6′,2″-terpyridine derivatives in high yields. Novel complexes with Gd(III), Fe(III) were obtained for these conjugates. Aggregation behaviour in solutions of different solubilisers was studied to inform the selection of the optimal solubilising platform for the porphyrins obtained; their photophysical and photochemical properties were also characterised. Micellar Pluronic F127 formulation was found to be the most effective solubiliser for stabilising the fluorescence-active monomolecular form of the photosensitisers (PS). In vitro cytotoxicity of the compounds was studied on the HEP-2 cell line with and without irradiation for 1.5 and 24 h. As a result, the IC50 of compounds 12 and 14 at an irradiation dose of 8.073 J/cm2 was shown to be 1.87 ± 0.333 and 1.4 ± 0.152 μM, respectively; without irradiation, the compound had no toxic effect within the studied concentration range (1.5 h). A test for the inhibition of metabolic cooperation or promoter activity was also performed for the abovementioned compounds, showing the efficacy and safety of the conjugates obtained. Preliminary data have indicated the high potential of the new type of PS to be promising molecular theranostic agents.