Prospects of Ruthenium(II) Polypyridyl Complexes for Application in Cystic Fibrosis Lung Airways: Influence of Environmental Conditions in Antimicrobial Photodynamic Therapy

Antimicrobial photodynamic therapy (aPDT) depends on a variety of characteristics of the photosensitizers (PSs) used, the pathogens to target and the involved environment. In a recent study using a series of Ruthenium(II) polypyridyl complexes ([Ru(II)]), we reported on the importance of the chemical structure of aPDT compounds on both their photo-physical/physico-chemical properties and their aPDT efficacy [1]. Under standard in vitro conditions, effective [Ru(II)]-mediated aPDT was demonstrated against planktonic cultures of Pseudomonas aeruginosa and Staphylococcus aureus strains that were isolated from the airways of Cystic Fibrosis (CF) patients. CF lung disease is characterized with many patho-physiological disorders that can compromise the effectiveness of antimicrobials. The presentation will expand significantly on our previously reported work [1], with the aim to further investigate [Ru(II)]-mediated aPDT under in vitro experimental settings, approaching the conditions of infected airways in CF patients. Thus, the isolated influence of a series of parameters (including increased osmotic strength, acidic pH, lower oxygen availability, etc.) on the properties of two selected [Ru(II)] complexes will be discussed [2]. Furthermore, these compounds were used to evaluate the possibility to photo-inactivate P. aeruginosa, while preserving an underlying epithelium of human bronchial epithelial cells. Altogether, our results provide substantial evidence for the relevance of [Ru(II)]-based aPDT in CF lung airways. Besides optimized nano-complexes, this study also highlights the various needs for translating such a challenging perspective into clinical practice.