2020, Ho, D.-K., Murgia, X., De Rossi, C., Christmann, R., Hüfner de Mello Martins, A.G., Koch, M., Andreas, A., Herrmann, J., Müller, R., Empting, M., Hartmann, R.W., Desmaele, D., Loretz, B., Couvreur, P., Lehr, C.-M.

Elimination of pulmonary Pseudomonas aeruginosa (PA) infections is challenging to accomplish with antibiotic therapies, mainly due to resistance mechanisms. Quorum sensing inhibitors (QSIs) interfering with biofilm formation can thus complement antibiotics. For simultaneous and improved delivery of both active agents to the infection sites, self-assembling nanoparticles of a newly synthesized squalenyl hydrogen sulfate (SqNPs) were prepared. These nanocarriers allowed for remarkably high loading capacities of hydrophilic antibiotic tobramycin (Tob) and a novel lipophilic QSI at 30 % and circa 10 %, respectively. The drug-loaded SqNPs showed improved biofilm penetration and enhanced efficacy in relevant biological barriers (mucin/human tracheal mucus, biofilm), leading to complete eradication of PA biofilms at circa 16-fold lower Tob concentration than Tob alone. This study offers a viable therapy optimization and invigorates the research and development of QSIs for clinical use.

2022, Jin, Minye, Gläser, Alisa, Paez, Julieta I.

Stimuli-responsive hydrogels are smart materials that respond to variations caused by external stimuli and that are currently exploited for biomedical applications such as biosensing, drug delivery and tissue engineering. The development of stimuli-responsive hydrogels with defined user control is relevant to realize materials with advanced properties. Recently, our group reported firefly luciferin-inspired hydrogel matrices for 3D cell culture. This platform exhibited advantages like rapid gelation rate and tunability of mechanical and biological properties. However, this first molecular design did not allow fine control of the gelation onset, which restricts application as a cell-encapsulating matrice with injectable and processable properties. In this article, we endow the firefly luciferin-inspired hydrogels with redox-triggering capability, to overcome the limitations of the previous system and to widen its application range. We achieve this goal by introducing protected macromers as hydrogel polymeric precursors that can be activated in the presence of a mild reductant, to trigger gel formation in situ with a high degree of control. We demonstrate that the regulation of molecular parameters (e.g., structure of the protecting group, reductant type) and environmental parameters (e.g., pH, temperature) of the deprotection reaction can be exploited to modulate materials properties. This redox-triggerable system enables precise control over gelation onset and kinetics, thus facilitating its utilization as an injectable hydrogel without negatively impacting its cytocompatibility. Our findings expand the current toolkit of chemically-based stimuli-responsive hydrogels.