Nanostructured photosensitizer based on a tetracationic derivative of bacteriochlorin for antibacterial photodynamic therapy

G.A Meerovich,N.I Philipova,I.G Tiganova,Yu.M Romanova,V.B Loschenov,E.A Makarova,E.A Lukianets,E.V Akhlyustina,I.D Romanishkin,N.V Alekseeva

doi:10.24075/brsmu.2018.087

Abstract

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-Py4BSHp4Br4, 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.

Highlights

Задача повышения эффективности антибактериальной ФДТ делает актуальными создание и исследование фотосенсибилизаторов (ФС) на основе поликатионных синтетических бактериохлоринов
By studying the dependence of 3-Py4BCHp4Br4 absorption on its concentration in the nanodispersion, we aimed to evaluate the severity of the aggregation process
In contrast to polycationic phthalocyanines, there are no expressed signs of aggregation in the absorption spectra of the 3-Py4BСHp4Br4 dispersion [15]: the shape of the absorption spectrum does not change as the concentration grows; the dependence of optical density on molar concentration is linear (Bouguer law satisfied) and consistent with the extinction values determined at low concentrations (Fig. 1)

Summary

Introduction

Задача повышения эффективности антибактериальной ФДТ делает актуальными создание и исследование фотосенсибилизаторов (ФС) на основе поликатионных синтетических бактериохлоринов. ОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕ НАНОМЕДИЦИНА has an additional structural element, a 10–15 nm thick outer membrane, which is heterogeneous and consists of porin proteins, lipopolysaccharide trimers and lipoproteins that build an external pseudo-surface of densely packed negative charges [9,10,11]. Such a system prevents the humoral protective factors from penetrating and enables resistance to many drugs: only relatively hydrophilic compounds with a molecular weight below 700 Da diffuse through the porin channels, and as the size and weight of the molecules grow, the probability of their diffusion into Gram-negative bacteria decreases. Cationic PS have another advantage: their highly concentrated aqueous compositions (solutions or nanodispersions) can be used for sensitization, since the Coulomb repulsion of molecules of cationic bacteriochlorins negatively affects their aggregation [12] and improves the efficacy of the photodynamic processes

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Conclusion