Liquid crystalline lipid nanoparticle promotes the photodynamic activity of gallium protoporphyrin against S. aureus biofilms.

Antimicrobial photodynamic therapy (aPDT) has emerged as an innovative strategy to combat antibiotic resistant microbes; yet aPDT efficacies against biofilms are sub-optimal due to inability of photosenstizers to reach microbes embedded in biofilm matrix. To overcome this challenge, liquid crystal lipid nanoparticles (LCNP) were employed in this study as a smart, biocompatible and triggerable delivery system for the new photosensitizer gallium protoporphyrin (GaPP), due to their capabilities in promoting efficient antimicrobial delivery to biofilms. The relationship between GaPP loading of LCNP, reactive oxygen species (ROS) production and the in vitro antibacterial activity against two antibiotic resistant Staphylococcus aureus strains was established. LCNP substantially improved the antibacterial activity of GaPP, completely eradicating S. aureus and MRSA planktonic cultures, using a GaPP concentration of 0.8 μM and light dose 1.9 J/cm2. At the same concentration and light dose, unformulated GaPP triggered only a 4 log10 and 2 log10 reduction in respective planktonic cultures. Most importantly, the activity of GaPP against biofilms was enhanced by 2-fold compared to unformulated GaPP, reducing the viability of S. aureus and MRSA biofilms by 8 log10 and 5 log10, respectively. The biosafety of photoactivated GaPP-LCNP was evaluated against human fibroblasts, which indicated a high safety profile of the treatment. Therefore, these findings encourage further investigations of GaPP-LCNP as a potential treatment for localized chronic infections.