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

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Abstract

Antimicrobial photodynamic therapy (aPDT) depends on a variety of parameters notably related to the photosensitizers used, the pathogens to target and the environment to operate. In a previous study using a series of Ruthenium(II) polypyridyl ([Ru(II)]) complexes, we reported the importance of the chemical structure on both their photo-physical/physico-chemical properties and their efficacy for aPDT. By employing standard in vitro conditions, effective [Ru(II)]-mediated aPDT was demonstrated against planktonic cultures of Pseudomonas aeruginosa and Staphylococcus aureus strains notably isolated from the airways of Cystic Fibrosis (CF) patients. CF lung disease is characterized with many pathophysiological disorders that can compromise the effectiveness of antimicrobials. Taking this into account, the present study is an extension of our previous work, with the aim of further investigating [Ru(II)]-mediated aPDT under in vitro experimental settings approaching the conditions of infected airways in CF patients. Thus, we herein studied the isolated influence of a series of parameters (including increased osmotic strength, acidic pH, lower oxygen availability, artificial sputum medium and biofilm formation) on the properties of two selected [Ru(II)] complexes. Furthermore, these compounds were used to evaluate the possibility to photoinactivate 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.

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Photodynamic therapy – mechanisms, photosensitizers and combinations

Krzysztof Kotowski, Olga Michel, Dawid Przystupski … (2018)

Photodynamic therapy (PDT) is a modern and non-invasive form of therapy, used in the treatment of non-oncological diseases as well as cancers of various types and locations. It is based on the local or systemic application of a photosensitive compound - the photosensitizer, which is accumulated in pathological tissues. The photosensitizer molecules absorb the light of the appropriate wavelength, initiating the activation processes leading to the selective destruction of the inappropriate cells. The photocytotoxic reactions occur only within the pathological tissues, in the area of photosensitizer distribution, enabling selective destruction. Over the last decade, a significant acceleration in the development of nanotechnology has been observed. The combination of photosensitizers with nanomaterials can improve the photodynamic therapy efficiency and eliminate its side effects as well. The use of nanoparticles enables achievement a targeted method which is focused on specific receptors, and, as a result, increases the selectivity of the photodynamic therapy. The object of this review is the anticancer application of PDT, its advantages and possible modifications to potentiate its effects.

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Antibiotic resistance of bacteria in biofilms

Philip Stewart, J William Costerton (2001)

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Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review

Mansura Mulani, Ekta E. Kamble, Shital N. Kumkar … (2019)

The acronym ESKAPE includes six nosocomial pathogens that exhibit multidrug resistance and virulence: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. Persistent use of antibiotics has provoked the emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) bacteria, which render even the most effective drugs ineffective. Extended spectrum β-lactamase (ESBL) and carbapenemase producing Gram negative bacteria have emerged as an important therapeutic challenge. Development of novel therapeutics to treat drug resistant infections, especially those caused by ESKAPE pathogens is the need of the hour. Alternative therapies such as use of antibiotics in combination or with adjuvants, bacteriophages, antimicrobial peptides, nanoparticles, and photodynamic light therapy are widely reported. Many reviews published till date describe these therapies with respect to the various agents used, their dosage details and mechanism of action against MDR pathogens but very few have focused specifically on ESKAPE. The objective of this review is to describe the alternative therapies reported to treat ESKAPE infections, their advantages and limitations, potential application in vivo, and status in clinical trials. The review further highlights the importance of a combinatorial approach, wherein two or more therapies are used in combination in order to overcome their individual limitations, additional studies on which are warranted, before translating them into clinical practice. These advances could possibly give an alternate solution or extend the lifetime of current antimicrobials.