ISMN-loaded PLGA-PEG nanoparticles conjugated with anti-Staphylococcus aureus alpha-toxin inhibit Staphylococcus aureus biofilms in chronic rhinosinusitis

Background: Staphylococcus aureus biofilms were linked to negative postsurgical outcomes of chronic rhinosinusitis (CRS). This study aims to develop a targeted nanoparticle and characterize its bactericidal effects. Methods: The authors prepared ISMN-loaded poly-lactide-co-glycolide acid (PLGA) and polyethylene glycol (PEG) nanoparticles conjugated with anti-S. aureus alpha-toxin (AA; ISMN-PLGA-PEG-AA), and determined its bactericidal and toxic effects. The antibiofilm propriety of ISMN-PLGA-PEG-AA was further investigated in a sheep CRS model. Results: ISMN-PLGA-PEG-AA had no toxic effect, while ISMN, ISMN-PLGA-PEG and ISMN-PLGA-PEG-AA had significantly anti-S. aureus effects. The blood concentrations and mRNA levels in sinus tissues of IL-4, IL-8 and IFN-gamma in the sheep CRS model were significantly low. Conclusion: ISMN-PLGA-PEG-AA can effectively inhibit S. aureus biofilm, and is a promising drug for CRS treatment.