Novel Polymer-Based Photodynamic Therapy Following Aerosol Lung Delivery
The specific objective of this project is to significantly improve the treatment of infections with the WHO priority-1 pathogen P. aeruginosa, which is one of the most dangerous key multi-drug resistant bacteria, inside biofilms in the lungs. In particular, photodynamic therapy (PDT) will be expanded and significantly enhanced by highly active, novel PDT photosensitizers and by grafting these optimized photosensitizers onto polymer backbones and by encapsulation into on-demand release polymer vesicles.
This new combined approach will overcome the key drawback of conventional PDT, i.e. the limited solubility of PDT complexes, by safeguarding a high local concentration. In addition, the difficulties to administer neat active substances to the site of action across the pulmonary mucus and biofilms in patients with chronic pulmonary disease will be circumvented by exploiting the properties of low fouling polymers.
The key advantage of the thus refined PDT is the spatially targeted, and via irradiation dose afforded by a bronchoscope fiber device, well-controlled localized generation of highly reactive oxygen species, which kill pathogens in a non-selective manner, thereby preventing the build-up of new resistances. The approach relies on published proof-of-concept data of all partners and will be developed and validated using bacteria and cell culture models (including mucus and/or biofilms) as well as animal models of antimicrobial resistant pneumonia.
Particular attention will be paid to biodistribution following in vivo nebulization, to evaluate both elimination pathway(s) and potential release of active drugs into the environment. The novel TARGET-THERAPY approach affords a highly effective and especially spatially and temporally targeted in vivo treatment, which will be to the benefit of patients suffering from a wide range of medical conditions.
ANR funded project “TARGET-THERAPY”
2021-2024, granted to Dr Tony LE GALL and Prof Holger SCHÖNHERR, 2nd French-German call for projects on antimicrobial resistance 2020 “One Health: AMR in environmental reservoirs and colonizing antibiotic resistant bacteria”
From April 1st, 2021 to March 31, 2024