To this day, any photosensitizers for the photodynamic treatment of pulmonary illnesses have been administered intravenously. There is, however, an intrinsic difficulty in reaching the target cells or bacteria in the respiratory system. Nebulization could overcome distribution problems and alleviate side effects by delivering the photosensitizers directly to the lungs. In this study, we evaluated the viability of three photosensitizers (indocyanine green, the chlorine Photodithazine®, and the porphyrin Photogem®) was evaluated comparatively in a jet nebulizer. Quantitative analysis was performed by looking at the droplet size, extent of nebulization, output over time, and stability of the solutions. All of the tested photosensitizers were found to be adequately nebulized. We also demonstrated the delivery of indocyanine green to the pulmonary tract and its activation with infrared light in a murine model using extracorporeal detection of fluorescence. This was an important step towards clinical implementation of the extracorporeally-illuminated photodynamic inactivation of pneumonia, recently demonstrated in vivo by this research group. This article is protected by copyright. All rights reserved.

The widespread use of antibiotics drives the evolution of antimicrobial-resistant bacteria (ARB), threatening patients and healthcare professionals. Therefore, the development of novel strategies to combat resistance is recognized as a global healthcare priority. The two methods to combat ARB are development of new antibiotics or reduction in existing resistances. Development of novel antibiotics is a laborious and slow-progressing task that is no longer a safe reserve against looming risks. In this research, we suggest a method for reducing resistance to extend the efficacious lifetime of current antibiotics. Antimicrobial photodynamic therapy (aPDT) is used to generate reactive oxygen species (ROS) via the photoactivation of a photosensitizer. ROS then nonspecifically damage cellular components, leading to general impairment and cell death. Here, we test the hypothesis that concurrent treatment of bacteria with antibiotics and aPDT achieves an additive effect in the elimination of ARB. Performing aPDT with the photosensitizer methylene blue in combination with antibiotics chloramphenicol and tetracycline results in significant reductions in resistance for two methicillin-resistant Staphylococcus aureus (MRSA) strains, USA300 and RN4220. Additional resistant S. aureus strain and antibiotic combinations reveal similar results. Taken together, these results suggest that concurrent aPDT consistently decreases S. aureus resistance by improving susceptibility to antibiotic treatment. In turn, this development exhibits an alternative to overcome some of the growing MRSA challenge.

Antibiotic-resistant bacteria, which are growing at a frightening rate worldwide, has put the world on a long-standing alert. The COVID-19 health crisis reinforced the pressing need to address a fast-developing pandemic. To mitigate these health emergencies and prevent economic collapse, cheap, practical, and easily applicable infection control techniques are essential worldwide. Application of light in the form of photodynamic action on microorganisms and viruses has been growing and is now successfully applied in several areas. The efficacy of this approach has been demonstrated in the fight against viruses, prompting additional efforts to advance the technique, including safety use protocols. In particular, its application to suppress respiratory tract infections and to provide decontamination of fluids, such as blood plasma and others, can become an inexpensive alternative strategy in the fight against viral and bacterial infections. Diverse early treatment methods based on photodynamic action enable an accelerated response to emerging threats prior to the availability of preventative drugs. In this review, we evaluate a vast number of photodynamic demonstrations and first-principle proofs carried out on viral control, revealing its potential and encouraging its rapid development toward safe clinical practice. This review highlights the main research trends and, as a futuristic exercise, anticipates potential situations where photodynamic treatment can provide a readily available solution.

In the context of the rapid increase of antibiotic-resistant infections, in particular of pneumonia, antimicrobial photodynamic therapy (aPDT), the microbiological application of photodynamic therapy (PDT), comes in as a promising treatment alternative since the induced damage and resultant death are not dependent on a specific biomolecule or cellular pathway. The applicability of aPDT using the photosensitizer indocyanine green with infrared light has been successfully demonstrated for different bacterial agents in vitro, and the combination of pulmonary delivery using nebulization and external light activation has been shown to be feasible. However, there has been little progress in obtaining sufficient in vivo efficacy results. This study reports the lung surfactant as a significant suppressor of aPDT in the lungs. In vitro, the clinical surfactant Survanta® reduced the aPDT effect of indocyanine green, Photodithazine®, bacteriochlorin-trizma, and protoporphyrin IX against Streptococcus pneumoniae . The absorbance and fluorescence spectra, as well as the photobleaching profile, suggested that the decrease in efficacy is not a result of singlet oxygen quenching, while a molecular dynamics simulation showed an affinity for the polar head groups of the surfactant phospholipids that likely impacts uptake of the photosensitizers by the bacteria. Methylene blue is the exception, likely because its high water solubility confers a higher mobility when interacting with the surfactant layer. We propose that the interaction between lung surfactant and photosensitizer must be taken into account when developing pulmonary aPDT protocols.

Photodynamic inactivation (PDI) is a promising alternative for combating infections caused by antimicrobial resistant bacteria. Pneumonias are among the most worrisome infections because of their high-mortality rate. Previous studies have demonstrated the feasibility of using PDI with extracorporeal light to treat pneumonia. In this study, we analyzed key parameters for the viability of this treatment, including the selectivity of the photodynamic response for pathogens over host cells. Our results showed that PDI can induce killing of Staphylococcus aureus (of up to 4.18 log for the strain Xen29 and 3.62 log for Xen36) under conditions where little or no toxicity for host cells is observed. We validated pulmonary delivery of the photosensitizer and light in mice, using photobleaching as an indicator, and demonstrated preservation of healthy tissues as evidence of the safety of the protocol. Overall, PDI displays low toxicity on host tissues, making it a promising tool for treatment of pneumonias caused by S. aureus and other important pathogens.

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The management of biofilm-related infections is a challenge in healthcare, and antimicrobial photodynamic therapy (aPDT) is a powerful tool that has demonstrated a broad-spectrum activity. Nanotechnology has been used to increase the aPDT effectiveness by improving the photosensitizer’s delivery properties. NewPS is a simple, versatile, and safe surfactant-free nanoemulsion with a porphyrin salt shell encapsulating a food-grade oil core with promising photodynamic action. This study evaluated the use of NewPS for aPDT against microorganisms in planktonic, biofilm, and in vivo models of infected wounds. First, the potential of NewPS-mediated aPDT to inactivate Streptococcus pneumoniae and Staphylococcus aureus suspensions was evaluated. Then, a series of protocols were assessed against S. aureus biofilms by means of cell viability and confocal microscopy. Finally, the best biofilm protocol was used for the treatment of S. aureus in a murine-infected wound model. A high NewPS-bacteria cell interaction was achieved since 0.5 nM and 30 J/cm 2 was able to kill S. pneumoniae suspension. In the S. aureus biofilm, enhanced efficacy of NewPS-aPDT was achieved when 100 µM of NewPS was applied with longer periods of incubation at the light dose of 60 J/cm 2 . The best single and double-session protocol reduced 5.56 logs and 6.03 logs, respectively, homogeneous NewPS distribution, resulting in a high number of dead cells after aPDT. The in vivo model showed that one aPDT session enabled a reduction of 6 logs and faster tissue healing than the other groups. In conclusion, NewPS-aPDT may be considered a safe and effective anti-biofilm antimicrobial photosensitizer.

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