Photoantimicrobials—So what's stopping us?

doi:10.1016/j.pdpdt.2009.10.007

Photodiagnosis and Photodynamic Therapy

Volume 6, Issues 3–4, September–December 2009, Pages 167-169

https://doi.org/10.1016/j.pdpdt.2009.10.007 Get rights and content

Summary

In the face of increasing multi-drug resistant bacteria, both in healthcare and the community, new drugs or novel methods of decontamination are required. The use of light-activated drugs – photoantimicrobials – has been promoted at various points during the past decade or more but has not yet gained meaningful clinical acceptance. Photoantimicrobials offer advantages over conventional drugs in attacking bacteria at various sites, rather than just one, and in the intermediacy of reactive oxygen species, against which there is little possibility of resistance.

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Lasers and light sources for PDT: past, present and future
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There are more references available in the full text version of this article.

Cited by (41)

The effect of femtosecond laser irradiation on the growth kinetics of Staphylococcus aureus: An in vitro study
2021, Journal of Photochemistry and Photobiology B: Biology
Citation Excerpt :
Since the rate of acquisition of resistance is faster than the clinical introduction of new antibiotics, the development of alternative antimicrobial techniques to treat these infections is becoming necessary for public health throughout the world [7–9]. One promising candidate is laser-based antimicrobial therapy (lbAT) [10,11] which is actively being studied for the treatment of such infections [12,13]. lbAT is a simple, non-invasive, and low-cost therapeutic approach causing no significant tissue damage [14].
We investigated the effect of femtosecond laser irradiation on the growth kinetics of Staphylococcus aureus. In order to improve laser-based antimicrobial therapy and develop a clinically viable modality, various laser parameters such as laser light wavelength, laser power, exposure time, and energy density were studied. The INSPIRE HF100 laser system (Spectra Physics) provided the femtosecond laser light, which was pumped by a mode-locked femtosecond Ti: sapphire laser MAI TAI HP (Spectra Physics). The survival of the bacterial cells was monitored after irradiation by determination of growth rate using optical density, which is a rapid, simple, and reliable method. The growth rate of laser-exposed cultures was compared to control cultures. Fifteen minutes of exposure to femtosecond laser radiation with a wavelength of 390 nm and 400 nm at an average power of 50 mW was enough to significantly reduce bacterial viability, with a lag in the growth phase of 5 h longer than the control culture (P < 0.0001 by ANOVA and Tukey test).
The application of antimicrobial photodynamic inactivation on methicillin-resistant S. aureus and ESBL-producing K. pneumoniae using porphyrin photosensitizer in combination with silver nanoparticles
2021, Photodiagnosis and Photodynamic Therapy
Citation Excerpt :
The advantages of local aPDI inactivation are low toxicity of the used light-activated substances (photosensitizers, PS) and the short time needed for treatment. In addition, the aPDI would appear as a method appropriate for treatment of chronic and persistent infections [10,11]. The mechanism of aPDI is the same as photodynamic therapy (PDT) in principle.
As resistance of bacterial strains to antibiotics is a major problem, there is a need to look for alternative treatments. One option is antimicrobial photodynamic inactivation (aPDI). The pathogenic cells are targeted by a nontoxic photosensitizer while the surrounding healthy tissue is relatively unaffected. The photosensitizer is activated by light of t appropriate wavelength resulting in the generation of reactive oxygen species that are cytotoxic for the pathogens.
In this work, the photosensitizer TMPyP and silver nanoparticles (AgNPs) were investigated for their synergistic antibacterial effect. We tested these two substances on two bacterial strains, methicillin-resistant Staphylococcus aureus 4591 (MRSA) and extended-spectrum beta-lactamases-producing Klebsiella pneumoniae 2486 (ESBL-KP), to compare their effectiveness. The bacteria were first incubated with TMPyP for 45 min or 5 h, then irradiated with a LED source with the total fluence of 10 or 20 J/cm² and then placed in a microbiological growth medium supplemented with AgNPs. To accomplish the synergistic effect, the optimal combination of TMPyP and AgNPs was estimated as 1.56–25 μM for TMPyP and 3.38 mg/l for AgNPs in case of MRSA and 1.56–50 μM for TMPyP and 3.38 mg/l for AgNPs in case of ESBL-KP at 45 min incubation with TMPyP and fluence of 10 J/cm². Longer incubation and/or longer irradiation led to a decrease in the maximum values of the photosensitizer concentration to produce the synergistic effect.
From this work it can be concluded that the combination of antimicrobial photodynamic inactivation with a treatment including silver nanoparticles could be a promising approach to treat bacterial infection.
Does PDT have potential in the treatment of COVID 19 patients?
2020, Photodiagnosis and Photodynamic Therapy
The corona virus pandemic has ignited a proliferation of research aimed at prevention of spread, early diagnosis and treatment.
Coincidentally, in recent years the Yorkshire Laser Centre has been engaged in developing the methodology of applying PDT in chronic bronchiectasis. Our methodology is based on Methylene Blue (MB) mediated PDT used topically within the airway.
The novelty of the method is the use of a nebulizer to deliver the photosensitizer.
We suggest that our protocol and methodology could be modulated for use in respiratory infections of COVID -19.
PDT- versus – Superbugs: The clinical struggle
2019, Photodiagnosis and Photodynamic Therapy
Nanocarriers for Photosensitizers for Use in Antimicrobial Photodynamic Therapy
2017, Nanostructures for Antimicrobial Therapy: Nanostructures in Therapeutic Medicine Series
Antimicrobial photodynamic therapy (aPDT) employs a photoreactive dye photosensitizer in combination with visible light and molecular oxygen. Following light absorption, the photochemical reactions lead to the generation of reactive oxygen species (ROS). ROS-mediated damage to proteins and lipids impairs function of the bacterial cellular structures and subsequently causes the eradication of microorganisms. aPDT is gaining increasing attention because of the multitargeted nature of the photosensitization process and resulting nonspecific mechanism of action. aPDT is effective against, e.g., bacteria, fungi, yeasts, and parasites including antibiotic-resistant strains. Numerous photosensitizers aggregate in aqueous environments, leading to attenuation of their photochemical activity and hindering of their cell internalization. Nanocarriers improve photosensitizer internalization by microbial cells and enable the biofilm barrier to be crossed, enhancing the inactivation of kinetics. Some nanocarriers improve photosensitizers’ ROS yield or act as photosensitizers themselves. This chapter aims to present the advantages of various nanoparticulate delivery systems for photosensitizers and to review different delivery strategies.
Visible light induced antibacterial properties of a Ru(II)–Pt(II) bimetallic complex
2017, Inorganica Chimica Acta
Citation Excerpt :
Although PDT is selectively activated via an external light stimulus, bioactivity depends on the PSs cellular association as 1O2 and other reactive oxygen species have limited lifetimes and/or diffusion radii [10]. The differences between Gram-positive (thick peptidoglycan structure) and Gram-negative (highly organized, multi-layer structure) morphologies and the emergence of antibiotic drug resistance have resulted in the necessity for a broad-spectrum antibiotic that overcomes these limitations [11–13]. As previously mentioned, PDT is a fundamentally different mode of bioactivity, which should overcome standard bacterial drug developed resistance, and can be improved through the incorporation of a cellular specific targeting mechanism.
The development of antibiotics with new modes of action and specificity are necessary with the emergence of multidrug resistant Gram-negative bacteria. Antimicrobial photodynamic therapy (aPDT) affords reactive oxygen species, which generally overcomes the conventional bacterial resistance mechanisms, but typical aPDT agents do not strongly associate with Gram-negative bacteria. However, by covalently coupling a Ru-based chromophore with a cis-PtCl₂ bioactive site, covalent interactions with the cell at the Pt moiety provides localization of the singlet oxygen generating chromophore. Reported here is the photoinhibition and photocytotoxicity of Escherichia coli, using the mixed-metal complex [Ru(Ph₂phen)₂(dpp)PtCl₂]²⁺ (Ph₂phen = 4,7-diphenyl-1,10-phenanthroline and dpp = 2,3-bis(2-pyridyl)pyrazine) in the presence of oxygen and low energy visible light. The Ru(II)–Pt(II) bimetallic complex shows promise as a photoactivated antibacterial agent that interacts with cells in a fundamentally different mode of action than cisplatin.

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Photodiagnosis and Photodynamic Therapy

Summary

References (8)

Serious infections due to methicillin-resistant Staphylococcus aureus: an evolving challenge for physicians

Eur J Intern Med

Ertapenem resistance and the Enterobacteriaceae

Int J Antimicrob Agents

Inactivation of catalase and superoxide dismutase by singlet oxygen derived from photoactivated dye

Biochimie

Lasers and light sources for PDT: past, present and future

Photodiag Photodyn Ther

Cited by (41)

The effect of femtosecond laser irradiation on the growth kinetics of Staphylococcus aureus: An in vitro study

The application of antimicrobial photodynamic inactivation on methicillin-resistant S. aureus and ESBL-producing K. pneumoniae using porphyrin photosensitizer in combination with silver nanoparticles

Does PDT have potential in the treatment of COVID 19 patients?

PDT- versus – Superbugs: The clinical struggle

Nanocarriers for Photosensitizers for Use in Antimicrobial Photodynamic Therapy

Visible light induced antibacterial properties of a Ru(II)–Pt(II) bimetallic complex