This work presents the results of studies of the features, mechanisms and effectiveness of the photodynamic effect of PS based on polycationic derivatives of long-wave phthalocyanines and synthetic bacteriochlorin on bacteria, bacterial biofilms, tumor cells and experimental animal tumor model.

Antibacterial photodynamic therapy (APDT) is a promising method of treatment of local infections, based on photochemical reaction of photosensitizer (PS) under irradiation with visible or near infra-red light of appropriate wavelength. A molecule of PS is activated by light energy and as a result singlet oxygen and other reactive oxygen species, which are toxic for microbes, are generated. Antibacterial action of new PS (synthetic polycationic bacteriochlorin derivatives with spectral maximum of absorbance at 760 nm) with improved features was investigated in vitro in this work. Tetra- and octacationic bacteriochlorins with lower molecular mass, as compared with ones previously proposed, turned out to be highly effective against Pseudomonas aeruginosa and Staphylococcus aureus in plankton and biofilm state: reduction of viable bacteria in biofilms reached 5log(10). The dependence of the effect on PS concentration, the time of incubation with PS and light dose was ascertained. Light microscopy of biofilms after photodynamic treatment and Live/Dead staining confirmed the death of bacteria or damage of their membranes after exposure to PS and irradiation.

The aim of this work is the study of antibacterial photodynamic inactivation (APDI) of Escherichia coli (on the example of a model E. coli K12 TG1), the influence of the charge of photosensitizer (PS) molecules on the efficiency of binding with these Gram-negative bacteria. The results obtained confirm that PSs based on polycationic phthalocyanines and synthetic bacteriochlorins provide effective photodynamic inactivation of E. coli, much higher than monocationic methylene blue and electro-neutral bacteriochlorin derivative. The efficiency of APDI, assessed by the intensity of bioluminescence of model E. coli K12 TG1 bacteria, correlates with the charge of PS molecules and the efficiency of electrostatic binding of PS to bacterial cells.

Abstract Antibacterial photodynamic therapy is a promising method of treating local infected foci, especially surgical and burn wounds, trophic and diabetic ulcers. This work explores the photophysical and antibacterial properties of novel phthalocyanine- and synthetic-bacteriochlorin-based octacationic photosensitizers (PS). The results of the study confirm their low degree of aggregation at high concentrations, as well as high efficiency of photodynamic treatment of Gram-negative bacterial biofilms.

Antibacterial photodynamic therapy (APDT) is a promising method of treating local infected foci, in particular, surgical and burn wounds, trophic and diabetic ulcers. Photodynamic inactivation (PDI) is able to effectively destroy bacterial cells without them developing resistance in response to treatment. This work was dedicated to the study of photophysical and antibacterial properties of new photosensitizers (PS) based on polycationic phthalocyanines and synthetic bacteriochlorins for photodynamic inactivation of P. aeruginosa bacteria and their biofilms. Gram-negative bacteria P. aeruginosa are often found in infected wounds, presumably in biofilm state and are characterized by rather low susceptibility to APDT, which is a problem. PS were studied for possible aggregation at various concentrations by means of absorption and fluorescence spectroscopy. The results of studies of the ZnPcChol8, (3-PyHp)4BCBr4 and (3-PyEBr)4BCBr4 in water and serum confirm the assumption of a low degree of their aggregation at high concentrations. Consequently, their photodynamic efficiency is high enabling to use these PS at high concentrations to sensitize pathological foci for APDT. It was shown that all the investigated PS had a high efficiency of photodynamic inactivation of Gram-negative bacteria P. aeruginosa, as well as their biofilms. Tetracationic hydrophilic near-infrared photosensitizer (3-PyEBr)4BCBr4 with reduced molecule size had significantly higher efficacy of photodynamic inactivation of P. aeruginosa biofilms compared with other studied photosensitizers.

The treatment of infected, long-term, non-healing, complicated wounds of the skin and mucosa, trophic ulcers, pressure sores and ulcers of diabetic feet represents a serious problem, especially in the case of resistant and multi-resistant pathogens. Antibacterial photodynamic therapy can be a promising method of local infected foci treatment of such diseases. This work is devoted to the study of the possibility of photodynamic inactivation (PDI) of Pseudomonas aeruginosa bacteria in the form of biofilms with the help of new polycationic photosensitizers (PSs) based on octacationic phthalocyanine and tetra- and octabacteriochlorins (ZnPcChol8, (3-PyBrE)4BCBr4 and (3-PyEPy)4BCBr8). More specifically, this work aims to clarify the role of light irradiation in PDI with the participation of new PSs, which has not been fully studied, especially with respect to the comparison of different PS types.

Polycationic derivatives of synthetic bacteriochlorin with absorption in the near infrared range are promising for the creation of photosensitizers (PS) for antimicrobial photodynamic therapy. In the present work, the photophysical and antibacterial properties of PS based on tetracationic derivatives of synthetic bacteriochlorins: hydrophilic 3-Py4BC(EtBr)4Br4 in aqueous solution and amphiphilic 3-Py4BCHP4Br4 in the dispersion of Kolliphor ELP were studied. Analysis of absorption and fluorescence in a wide range of concentrations has demonstrated low aggregation of the PS over the entire range. A high efficiency of photodynamic inactivation of Gram-positive Staphylococcus aureus and Gramnegative Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii bacteria was observed.

Cationic bacteriochlorin derivatives which molecules differing by lipophilicity and positive charge degree have been investigated in vitro as photosensitizers for photodynamic inactivation of biofilm bacteria.

Bacteriochlorins as the antimicrobial photosensitizers have a promising future in the face of the unrelenting increase in antimicrobial resistance. The goal of this study was to investigate the infl uence of lipophilicity and number of positively charged substituents in these molecules on the photodynamic inactivation (PDI) of biofi lm bacteria in vitro. Testing how bacteriochlorin derivatives with different properties affect microbes will allow to determine the optimal ratio of these parameters within a single molecule. We have investigated 4 bacteriochlorin derivatives, all of which were synthesized in Organic Intermediates and Dyes Institute. These were: hydrophobic neutral meso-tetra(3-pyridyl) bacteriochlorin (ВС1), amphyphilic tetracationic meso-tetra(1- undecyl-3-pyridyl)bacteriochlorin tetrabromide (ВС2), hydrophilic tetracationic meso-tetra[1-(4'-bromobutyl)-3-pyridyl]bacteriochlorin tetrabromide (ВС3) and octacationic meso-tetra[1-(4'-pyridiniobutyl) -3-pyridyl]bacteriochlorin octabromide (ВС4) . The water-soluble cationic bacteriochlorin derivatives showed the most effective PDI of bacteria in biofi lms. While tetracationic BC3 caused total inactivation of S. aureus 15, octacationic BC4 was bactericidal for P. aeruginosa 32 to the same degree (>99.999%). Interestingly, increasing the number of cationic substituents from 4 to 8 in bacteriochlorin molecules enhances bactericidal action against gram-negative bacteria in biofi lms. The lack of charge-carrying groups and high degree of lipophilicity of PS have negative impact on PDI of biofi lm bacteria. Bacterial membrane damage as a result of PDI can be one of the causes of cell death.

Задача повышения эффективности антибактериальной ФДТ делает актуальными создание и исследование фотосенсибилизаторов (ФС) на основе поликатионных синтетических бактериохлоринов. Целью настоящей работы было изучить в широком диапазоне концентраций фотофизические и антибактериальные свойства наноструктурированного ФС на основе 3-Py4BСHp4Br4, тетракатионного амфифильного производного синтетического бактериохлорина. Наноструктурированную дисперсию ФС получили путем его солюбилизации в 4%-м Kolliphor ELP (BASF). Исследование интенсивности и формы спектров поглощения и флуоресценции в диапазоне концентраций от 0,001 до 0,2 мМ продемонстрировало низкую агрегацию этого ФС во всем диапазоне и высокую эффективность фотодинамической инактивации грамположительных бактерий S. aureus и грамотрицательных бактерий P. aeruginosa и K. pneumoniae.

Making antibacterial PDT more effective is a task that calls for the development of photosensitizers (PS) based on polycationic synthetic bacteriochlorins and subsequent analysis of properties of such photosensitizers. This study aimed to explore photophysical and antibacterial properties of the nanostructured PS based on 3-Py(4)BSHp(4)Br(4), tetracationic amphiphilic derivative of synthetic bacteriochlorin. The PS was solubilized in a 4% Kolliphor ELP to obtain its nanostructured dispersion. We researched the absorption and fluorescence spectra intensity and profiles, studying concentrations from 0.001 to 0.2 mM, and found that the aggregation level of the PS in question is low throughout the range investigated while the S. aureus (gram-positive) and P. aeruginosa and K. pneumoniae (gram-negative) PD inactivation effectiveness is high.

Bacteriochlorins as the antimicrobial photosensitizers have a promising future in the face of the unrelenting increase in antimicrobial resistance. The goal of this study was to investigate the infl uence of lipophilicity and number of positively charged  substituents in these molecules on the photodynamic inactivation  (PDI) of biofi lm bacteria in vitro. Testing how bacteriochlorin  derivatives with different properties affect microbes will allow to  determine the optimal ratio of these parameters within a single  molecule. We have investigated 4 bacteriochlorin derivatives, all of  which were synthesized in Organic Intermediates and Dyes Institute. These were: hydrophobic neutral meso-tetra(3-pyridyl)  bacteriochlorin (ВС1), amphyphilic tetracationic meso-tetra(1- undecyl-3-pyridyl)bacteriochlorin tetrabromide (ВС2), hydrophilic  tetracationic meso-tetra[1-(4'-bromobutyl)-3-pyridyl]bacteriochlorin  tetrabromide (ВС3) and octacationic meso-tetra[1-(4'-pyridiniobutyl) -3-pyridyl]bacteriochlorin octabromide (ВС4) . The water-soluble  cationic bacteriochlorin derivatives showed the most effective PDI of  bacteria in biofi lms. While tetracationic BC3 caused total inactivation of S. aureus 15, octacationic BC4 was bactericidal for P. aeruginosa  32 to the same degree (>99.999%). Interestingly, increasing the  number of cationic substituents from 4 to 8 in bacteriochlorin  molecules enhances bactericidal action against gram-negative  bacteria in biofi lms. The lack of charge-carrying groups and high  degree of lipophilicity of PS have negative impact on PDI of biofi lm  bacteria. Bacterial membrane damage as a result of PDI can be one of the causes of cell death.

This work is devoted to the study of two new synthetic bacteriochlorins with four and eight cationic substitutes as the photosensitizers in the photodynamic process. The spectral and antibacterial properties of these photosensitizers in saline solution were investigated. It is shown, that the aggregation ability decreases and the antibacterial efficiency grows as the cationic substitute number increases.