Interaction of peptide-loaded photocatalytic nanoparticles with bacterial membrane components - lipopolysaccharides

In the global fight against antimicrobial resistance, photocatalytic TiO2 nanoparticles (TiO2NPs) represent potent non-conventional antibiotics, capable of inducing oxidative degradation of bacterial membranes under UV illumination. However, the poor selectivity between bacteria and human cells severely limit their clinical translation. Recently, we demonstrated that loading TiO2NPs with antimicrobial peptides (AMPs), specifically the AMP LL-37, improves the selectivity between bacteria-like and eukaryotic-mimicking bilayers. Here, we will extend this investigation to other key components of bacterial cell walls, i.e. bacterial lipopolysaccharides (LPS), composing the outer cell membrane of Gram-negative bacteria. We will use Neutron Reflectometry to investigate the structural modification induced by bare TiO2NPs (control sample) and LL-37-TiO2NPs on either "smooth" or "rough" LPS surfaces (mimicking the two main phenotypes of bacterial LPS), under UV illumination. The results will provide mechanistic insights on the oxidative degradation of bacterial LPS by AMPs-loaded TiO2NPs and on how its susceptibility depends on the structure and composition of LPS layers.