Effects of isosorbide mononitrate loaded nanoparticles conjugated with anti- Staphylococcus aureus α-toxin on Staphylococcus aureus biofilms.

Staphylococcus aureus (S. aureus) is associated with recalcitrant chronic infection, especially in chronic rhinosinusitis (CRS). S. aureus infection and biofilms cause poorer postsurgical outcomes. We developed isosorbide mononitrate (ISMN) loaded nanoparticles conjugated with an anti-Staphylococcus aureus alpha-toxin (anti-S. aureus alpha-toxin) antibody that could target biofilms and investigated their anti-biofilm effect. Anti-S. aureus alpha-toxin antibody coupled immunoliposomes were generated. The effect of ISMN immunoliposomes on S. aureus biofilm formation and their anti-biofilm efficacy were examined using the crystal violet method and confocal laser scanning microscopy, respectively. Relative biofilm viability at 24 h was tested using the alamarBlue assay. The biofilm formation inhibitory effect on all concentrations of ISMN immunoliposomes was stronger than that of ISMN liposomes and free ISMN (P<0.05). At concentrations of 45 and 23 mg/ml, the inhibitory effect of ISMN liposomes was stronger than that of free ISMN (P<0.05), while at 11 mg/ml, the inhibitory effect of ISMN liposomes was the same as that of ISMN (P>0.05). At 45 and 23 mg/ml, the inhibitory effect of ISMN immunoliposomes on formed biofilms was greater than that of ISMN liposomes and free ISMN (P<0.05) and the inhibitory effect of ISMN liposomes was stronger than that of free ISMN (P<0.05). At 11 mg/ml, ISMN immunoliposomes, ISMN liposomes, and ISMN had the same effect on formed biofilms (P>0.05). In conclusion, ISMN immunoliposomes nearly completely destroy biofilm structure. ISMN immunoliposomes provide a promising approach for treating infectious diseases caused by S. aureus biofilms, including refractory CRS, chronic skin infection, sepsis, and osteomyelitis.