CC BY
3DOI 10.24412/cl-37136-2023-1-19-21
PHOTODYNAMIC THERAPY AND COMBINED TREATMENTS
AMANDA SURUR1, ANDREI DABUL1 AND CARLA FONTANA1
1 School of Pharmaceutical Sciences, Sao Paulo State University, Brazil
amanda.koberstain@unesp.br nicoli.dabul@unesp.br
ABSTRACT
Antimicrobial photodynamic therapy (aPDT) is a noninvasive form of therapy used in the treatment of diseases in various fields of medicine, such as dermatology [1,2], oncology [3,4] and urology [5,6]. Such treatment produces excellent therapeutic results alone, but there is also the possibility of applying combined therapy of aPDT with other therapeutic protocols aiming to improve the outcome [7]. aPDT still presents the advantage of being well tolerated by patients due to its selective action [8].
aPDT is based on the local or systemic application of a photosensitizing compound (PS), which is intensely accumulated in target tissues. Light at a specific wavelength then activates the PS from its ground state to the excited state, which will react with nearby molecules by transfer of energy or charges in two possible reactions: type I or type II (Fig. 1). Both pathways can cause oxidation of various cellular components, resulting in cell death. In the type I reaction there is production of free radicals, such as HO\ which reacts with either biomolecules or with other HO^ radicals, originating the cytotoxic compound hydrogen peroxide, besides lipoperoxide, leading to lipid peroxidation. In the type II reaction, energy is transferred to oxygen, inducing the production of 1O2, which leads to the oxidation of proteins, nucleic acids and lipids [7].
Ground singlet state
Figure 1: Jablonski's Diagram for the mechanism of action of PDT type I and II reactions. PS: photosensitizer; PSEs: photosensitizer in excited singlet state; PSEt: triplet excited state photosensitizer;
1O2: singlet oxygen. Adapted from [9].
One of the possible combined treatments mentioned is the employment of enzymatic inhibitors with subsequent photodynamic treatment. Recently, our research group was able to demonstrate that methylene blue-mediated aPDT in association with a superoxide dismutase inhibitor was effective in reducing the microbial viability of E. coli cultured both in planktonic and biofilm forms, characterizing a synergistic phenomenon. Thus, further studies evaluating this combined treatment against other pathogens that have
enzymatic mechanisms for oxidative damage prevention via reactive oxygen species production will be strengthened [10].
Another possibility of combined treatment would be the use of glycoside hydrolases to degrade the polysaccharide fraction of the extracellular matrix of the microbial biofilm, and then applying aPDT in order to reduce the viability of the microbial cells.
It is estimated that most microorganisms on the planet live in the form of biofilms, allowing them to survive in inhospitable environments. In the case of human pathogens, this feature is particularly important, as it makes the action of antimicrobials even more difficult. Furthermore, exposure to antimicrobial concentration gradients within the biofilm may facilitate the development of resistance [11]. Biofilms are communities of microorganisms that attach to biotic or abiotic surfaces through a polymeric extracellular matrix, which may contain polysaccharides, proteins, extracellular DNA and lipids, in addition to other biomolecules, with polysaccharides being the most abundant in most microorganisms [12].
There are several strategies to inhibit the formation of bacterial biofilms, or even to destroy preformed biofilms, and one of them is the use of enzymes that target the polymers of the extracellular matrix of biofilms, such as the glycoside hydrolases aiming the polysaccharides [13].
This is a very recent research line implemented in our laboratory, in collaboration with another research group, who already demonstrated the ability of these enzymes to eradicate bacterial biofilms. Thus, we intend to evaluate the action of several glycoside hydrolases on several microbial biofilms and further investigate their combination with aPDT aiming a deeper effect.
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