Terpyridine-Micelles for Inhibiting Bacterial Biofilm Development.

Iron plays a critical role in bacterial infections and is especially critical for supporting biofilm formation. Until recently, Fe(III) was assumed to be the most relevant form of iron to chelate in therapeutic antimicrobial strategies due to its natural abundance under normal oxygen and physiologic conditions. Recent clinical data obtained from cystic fibrosis (CF) patients found that there is actually quite an abundance of Fe(II) present in sputum and that there exists a significant relationship between sputum Fe(II) concentration and severity of the disease. A biocompatible mixed micelle formed from the self-assembly of poly(lactic- co-glycolic acid)- block-methoxy poly(ethylene glycol) (PLGA- b-mPEG) and poly(lactic- co-glycolic acid)- block-poly(terpyridine)5 [PLGA- b-p(Tpy)5] polymers was prepared to chelate Fe(II) (Tpy-micelle). Tpy-micelles showed high selectivity for Fe(II) over Fe(III), decreased biofilm mass more effectively under anaerobic conditions at >4 μM Tpy-micelles, reduced bacteria growth in biofilms by >99.9% at 128 μM Tpy-micelles, effectively penetrated throughout a 1-day old biofilm, and inhibited biofilm development in a concentration-dependent manner. This study reveals that Fe(II) chelating Tpy-micelles are a promising addition to Fe(III) chelating strategies to inhibit biofilm formation in CF lung infections.