Aerosol-based antimicrobial photoinactivation in the lungs: an action spectrum study

Chiara Treghini,Franco Fusi,Giovanni Romano,Alfonso Dell’Accio

doi:10.1007/s43630-021-00066-2

Chiara Treghini, Franco Fusi + Show 2 more

Open Access

https://doi.org/10.1007/s43630-021-00066-2

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Abstract

Chronic lung infections are among the most diffused human infections, being often associated with multidrug-resistant bacteria. In this framework, the European project “Light4Lungs” aims at synthesizing and testing an inhalable light source to control lung infections by antimicrobial photoinactivation (aPDI), addressing endogenous photosensitizers only (porphyrins) in the representative case of S. aureus and P. aeruginosa. In the search for the best emission characteristics for the aerosolized light source, this work defines and calculates the photo-killing action spectrum for lung aPDI in the exemplary case of cystic fibrosis. This was obtained by applying a semi-theoretical modelling with Monte Carlo simulations, according to previously published methodology related to stomach infections and applied to the infected trachea, bronchi, bronchioles and alveoli. In each of these regions, the two low and high oxygen concentration cases were considered to account for the variability of in vivo conditions, together with the presence of endogenous porphyrins and other relevant absorbers/diffusers inside the illuminated biofilm/mucous layer. Furthermore, an a priori method to obtain the “best illumination wavelengths” was defined, starting from maximizing porphyrin and light absorption at any depth. The obtained action spectrum is peaked at 394 nm and mostly follows porphyrin extinction coefficient behavior. This is confirmed by the results from the best illumination wavelengths, which reinforces the robustness of our approach. These results can offer important indications for the synthesis of the aerosolized light source and definition of its most effective emission spectrum, suggesting a flexible platform to be considered in further applications.

Highlights

In the context of antibiotic resistance (ABR), lung chronic infections are among the most affected worldwide [1,2,3]
Due to the primary role of endogenous porphyrins in aPDI, their concentration was varied of ± 1 order of magnitude respect to the chosen representative value (Table 1), maintaining all the other parameters constant
This work is related to the development of an innovative and inhalable light source in the form of a luminous aerosol, to control lung infections associated to the presence of S. aureus and/or P. aeruginosa

Summary

Introduction

In the context of antibiotic resistance (ABR), lung chronic infections are among the most affected worldwide [1,2,3]. The only available treatment for Chiara Treghini and Alfonso Dell’Accio have contributed to this work. In this context, both antimicrobial PDT (aPDT) and aPDI can play an important role in overcoming ABR, with or without the use of external photosensitizers and/or the contemporary use of antimicrobial compounds [7,8,9]. In human applications of aPDT, most results are either related to in vitro or ex vivo proof-of-principle experiments or concern the in vivo treatment of external organs, such as the case of skin and mucosal infections [10] due to the relative facility in designing and using illumination sources. PDT clinical applications in the case of internal organ diseases is

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