Gallium Protoporphyrin Liquid Crystalline Lipid Nanoparticles: A Third-Generation Photosensitizer against Pseudomonas aeruginosa Biofilms.

The looming antimicrobial resistance pandemic has encouraged the investigation of antimicrobial photodynamic therapy (aPDT) as a promising technology to combat recalcitrant bacterial infections caused by antibiotic resistant strains. Here, we report on the optimization and effective application of gallium protoporphyrin liquid crystalline lipid nanoparticles (GaPP-LCNP) as a photosensitizer for aPDT against the Gram-negative bacteria P. aeruginosa in both planktonic and biofilm modes of growth. LCNP significantly enhanced the performance of GaPP as photosensitizer by two-fold, which was correlated with higher antibacterial activity, reducing the viability of planktonic P. aeruginosa by 7 log 10 using 0.8 µM GaPP-LCNP and a light dose of 17 J.cm -2 . Importantly, GaPP-LCNP also reduced the viability of biofilms by 6 log 10 at relatively low light dose of 34.2 J.cm -2 using only 3 µM GaPP-LCNP. The high antibiofilm activity of GaPP-LCNP at low GaPP-LCNP dose indicated the high efficiency and safety profile of GaPP-LCNP as a promising platform for photodynamic inactivation of recalcitrant infections.