The role of the light source in antimicrobial photodynamic therapy

This work was financially supported by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant (agreement no. 764837) and NCN Opus grant no. 2019/35/B/ST4/03280. We are also grateful to the Engineering and Physical Sciences Research Council of the UK for financial support from grants EP/R511778/1 and EP/L015110/1.Antimicrobial photodynamic therapy (APDT) is a promising approach to fight the growing problem of antimicrobial resistance that threatens health care, food security and agriculture. APDT uses light to excite a light-activated chemical (photosensitiser), leading to the generation of reactive oxygen species (ROS). Many APDT studies confirm its efficacy in vitro and in vivo against bacteria, fungi, viruses and parasites. However, the development of the field is focused on exploring potential targets and developing new photosensitisers. The role of light, a crucial element for ROS production, has been neglected. What are the main parameters essential for effective photosensitiser activation? Does an optimal light radiant exposure exist? And finally, which light source is best? Many reports have described the promising antibacterial effects of APDT in vitro, however, its application in vivo, especially in clinical settings remains very limited. The restricted availability may partially be due to a lack of standard conditions or protocols, arising from the diversity of selected photosensitising agents (PS), variable testing conditions including light sources used for PS activation and methods of measuring anti-bacterial activity and their effectiveness in treating bacterial infections. We thus sought to systematically review and examine the evidence from existing studies on APDT associated with the light source used. We show how the reduction of pathogens depends on the light source applied, radiant exposure and irradiance of light used, and type of pathogen, and so critically appraise the current state of development of APDT and areas to be addressed in future studies. We anticipate that further standardisation of the experimental conditions will help the field advance, and suggest key optical and biological parameters that should be reported in all APDT studies. More in vivo and clinical studies are needed and are expected to be facilitated by advances in light sources, leading to APDT becoming a sustainable, alternative therapeutic option for bacterial and other microbial infections in the future.Publisher PDFPeer reviewe

Treatment of antibiotic-resistant bacteria colonizing diabetic foot ulcers by OLED induced antimicrobial photodynamic therapy

KM, KJP and IDWS were supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant (Agreement N°764837) and NCN Opus Grant No. 2019/35/B/ST4/03280.We evaluate the efficacy of antimicrobial Photodynamic Therapy (APDT) for inactivating a variety of antibiotic-resistant clinical strains from diabetic foot ulcers. Here we are focused on APDT based on organic light-emitting diodes (OLED). The wound swabs from ten patients diagnosed with diabetic foot ulcers were collected and 32 clinical strains comprising 22 bacterial species were obtained. The isolated strains were identified with the use of mass spectrometry coupled with a protein profile database and tested for antibiotic susceptibility. 74% of isolated bacterial strains exhibited adaptive antibiotic resistance to at least one antibiotic. All strains were subjected to the APDT procedure using an OLED as a light source and 16 µM methylene blue as a photosensitizer. APDT using the OLED led to a large reduction in all cases. For pathogenic bacteria, the reduction ranged from 1.1-log to > 8 log (Klebsiella aerogenes, Enterobacter cloaca, Staphylococcus hominis) even for high antibiotic resistance (MRSA 5-log reduction). Opportunistic bacteria showed a range from 0.4-log reduction for Citrobacter koseri to > 8 log reduction for Kocuria rhizophila. These results show that OLED-driven APDT is effective against pathogens and opportunistic bacteria regardless of drug resistance.Publisher PDFPeer reviewe

Flexible organic light-emitting diodes for antimicrobial photodynamic therapy

The authors are grateful to the European Research Council (grant 321305) and EPSRC (grant EP/L015110/1) for financial support. The authors would like to acknowledge EU grant Polythea (grant 764837) as well as support from the Polish Ministry of Science and Higher Education for the Faculty of Chemistry of WUT.Bacterial infection is a serious and growing problem as antibiotic resistance grows leading to patient suffering, death and increased costs of healthcare. To address this problem, we propose using flexible organic light-emitting diodes (OLEDs) as light sources for photodynamic therapy (PDT) to kill bacteria. PDT involves the use of light and a photosensitizer to generate reactive oxygen species that kill neighbouring cells. We have developed flexible top-emitting flexible OLEDs with the ability to tune the emission peak from 669-737 nm to match the photosensitizer, together with high irradiance, low driving voltage, long operational lifetime and adequate shelflife. These features enable OLEDs to be the ideal candidate for ambulatory PDT light sources. A detailed study of OLED-PDT for killing S. aureus was performed. The results show that our OLEDs in combination with the photosensitizer methylene blue can kill more than 99% of bacteria, which indicates a huge potential for using OLEDs to treat bacterial infections.Publisher PDFPeer reviewe

Flexible organic light-emitting diodes for antimicrobial photodynamic therapy

Bacterial infection is a serious and growing problem as antibiotic resistance grows leading to patient suffering, death and increased costs of healthcare. To address this problem, we propose using flexible organic light-emitting diodes (OLEDs) as light sources for photodynamic therapy (PDT) to kill bacteria. PDT involves the use of light and a photosensitizer to generate reactive oxygen species that kill neighbouring cells. We have developed flexible top-emitting flexible OLEDs with the ability to tune the emission peak from 669-737 nm to match the photosensitizer, together with high irradiance, low driving voltage, long operational lifetime and adequate shelflife. These features enable OLEDs to be the ideal candidate for ambulatory PDT light sources. A detailed study of OLED-PDT for killing S. aureus was performed. The results show that our OLEDs in combination with the photosensitizer methylene blue can kill more than 99% of bacteria, which indicates a huge potential for using OLEDs to treat bacterial infections

The role of the light source in antimicrobial photodynamic therapy

Antimicrobial photodynamic therapy (APDT) is a promising approach to fight the growing problem of antimicrobial resistance that threatens health care, food security and agriculture. APDT uses light to excite a light-activated chemical (photosensitiser), leading to the generation of reactive oxygen species (ROS). Many APDT studies confirm its efficacy in vitro and in vivo against bacteria, fungi, viruses and parasites. However, the development of the field is focused on exploring potential targets and developing new photosensitisers. The role of light, a crucial element for ROS production, has been neglected. What are the main parameters essential for effective photosensitiser activation? Does an optimal light radiant exposure exist? And finally, which light source is best? Many reports have described the promising antibacterial effects of APDT in vitro, however, its application in vivo, especially in clinical settings remains very limited. The restricted availability may partially be due to a lack of standard conditions or protocols, arising from the diversity of selected photosensitising agents (PS), variable testing conditions including light sources used for PS activation and methods of measuring anti-bacterial activity and their effectiveness in treating bacterial infections. We thus sought to systematically review and examine the evidence from existing studies on APDT associated with the light source used. We show how the reduction of pathogens depends on the light source applied, radiant exposure and irradiance of light used, and type of pathogen, and so critically appraise the current state of development of APDT and areas to be addressed in future studies. We anticipate that further standardisation of the experimental conditions will help the field advance, and suggest key optical and biological parameters that should be reported in all APDT studies. More in vivo and clinical studies are needed and are expected to be facilitated by advances in light sources, leading to APDT becoming a sustainable, alternative therapeutic option for bacterial and other microbial infections in the future

Porphyrin-Loaded Lignin Nanoparticles Against Bacteria: A Photodynamic Antimicrobial Chemotherapy Application

The need for alternative strategies to fight bacteria is evident from the emergence of antimicrobial resistance. To that respect, photodynamic antimicrobial chemotherapy steadily rises in bacterial eradication by using light, a photosensitizer and oxygen, which generates reactive oxygen species that may kill bacteria. Herein, we report the encapsulation of 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphyrin into acetylated lignin water-dispersible nanoparticles (THPP@AcLi), with characterization of those systems by standard spectroscopic and microscopic techniques. We observed that THPP@AcLi retained porphyrin's photophysical/photochemical properties, including singlet oxygen generation and fluorescence. Besides, the nanoparticles demonstrated enhanced stability on storage and light bleaching. THPP@AcLi were evaluated as photosensitizers against two Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, and against three Gram-positive bacteria, Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis. THPP@AcLi were able to diminish Gram-positive bacterial survival to 0.1% when exposed to low white LED light doses (4.16 J/cm2), requiring concentrations below 5 μM. Nevertheless, the obtained nanoparticles were unable to diminish the survival of Gram-negative bacteria. Through transmission electron microscopy observations, we could demonstrate that nanoparticles did not penetrate inside the bacterial cell, exerting their destructive effect on the bacterial wall; also, a high affinity between acetylated lignin nanoparticles and bacteria was observed, leading to bacterial flocculation. Altogether, these findings allow to establish a photodynamic antimicrobial chemotherapy alternative that can be used effectively against Gram-positive topic infections using the widely available natural polymeric lignin as a drug carrier. Further research, aimed to inhibit the growth and survival of Gram-negative bacteria, is likely to enhance the wideness of acetylated lignin nanoparticle applications