Nano-enabled stimuli-responsive scaffolds for targeted antimicrobials delivery to treat Staphylococcous aureus infections and restore skin homeostasis
About the project
Staphylococcus aureus is a major cause of superficial and invasive skin and soft tissue infection. The emergence of resistant S. aureus infections is a global problem that leads to difficult and prolonged treatment, long hospital stays and a huge financial burden on the health system. Upon emergence and establishment of infection, a communication process between S. aureus cells, termed quorum sensing (QS), regulates the production of virulence factors and the formation of antibiotic-resistant biofilms through the secretion of highly specific autoinducing signaling molecules (AIs).
TARDIS aims to develop innovative polymeric matrices loaded with nanoscale systems for targeted delivery of substances with i) high bactericidal efficacy against pathogenic S. aureus and ii) with the ability to restore the beneficial balance of the skin microbiome and, accordingly, the physiological functions for the treatment of chronic wounds. New antimicrobial lipids and peptides derived from algae will be used to produce nanogels and free-standing nanoparticles with low potential for resistance development. The nano-carriers will be incorporated into stimuli-responsive hydrogel 3D networks for targeted delivery of antimicrobial nano-actives to the site of infection, avoiding toxic effects on human cells and the beneficial skin microbiome. Taking advantage of the natural cell-to-cell communication principles of bacteria, QS signaling substances (AIs) or their inhibitors (QSIs) will be incorporated on the surface of the developed bactericide delivery nanosystems to direct the bactericidal payload to the target S. aureus while avoiding toxic effects on human cells and beneficial skin microbiota. QSI binding to the S. aureus receptor is expected to attenuate bacterial virulence and biofilm formation, allowing the killing effect of the cargo to occur at lower concentrations. Antimicrobial efficacy and specificity will be confirmed in vitro using mixed cultures of target bacteria and in vivo in mouse models. Microbiome balance will be assessed by metagenome analysis and the safety of the developed antibacterial delivery nanocarriers will be evaluated according to OECD guidelines. TARDIS will apply nano-engineering strategies to innovatively develop stable and efficient polymer matrices with bio-based nano-delivery systems, developing them from a ‘proof-of-concept’ technology readiness level (TRL2-3) to in vitro validation and at animal models (TRL4). The project envisages a dissemination and exploitation plan to turn the results into promising therapeutics for the treatment of difficult-to-treat infections.
Project partners
| Universitat Politecnica de Catalunya, Spain |  |
| Sofia University, Bulgaria |  |
| SINTEFF OCEAN, Norway |  |
| Marmara University, Turkey |  |
| Dead Sea and Arava Science Center, Israel |  |
More information could be find on the project website: https://tardisproject.eu/