The FET Open project "Inhalable Aerosol Light Source for Controlling Drug-Resistant Bacterial Lung Infections" (with acronym Light4Lungs and Grant agreement ID: 863102) proposes a novel approach to address the problem of antimicrobial resistance in the treatment of chronic lung infections, which are the leading cause of morbidity and mortality in patients with diseases such as cystic fibrosis and hospital-acquired lung infections.
The goal is to develop a novel therapeutic scheme for the treatment of the infections, replacing antibiotics by inhalable light sources that will excite bacterial endogenous photosensitizers (e.g. iron-free porphyrins), eliminating the pathogenic bacteria by the photodynamic effect (local production of cytotoxic reactive oxygen species by the combined action of light, a photosensitiser and oxygen) irrespective of its multidrug resistance profile. The aim is to have a safe treatment for the host tissue thanks to its lack of self-photosensitising ability.
Three main objectives are being pursued: (i) The design of the treatment components, based on biological models, aerosol-based light emitting particles, and the action spectrum of the photodynamic effect; (ii) the realisation of the treatment components, from the particles to the aerosol and to the mechanism of particle activation prior to inhalation; and (iii) the assessment of the treatment efficacy and safety using in vitro and in vivo models.
At the end of the project, proof of concept has been achieved: an inhalable light source has been developed that is devoid of any measurable toxicity against the lungs host tissue but inactivates bacteria through the emission of light. An stable aerosol formulation of the light-emitting particles has been developed for delivery to the lungs. The therapy components have been tested in a variety of in vitro, ex vivo and in vivo lung infections models and the mechanistic insight that has been gained has been used to boost the efficiency of the bacterial photoinactivation process. The main barriers for clinical translation of the light therapy have been identified.
