Antibiotic-loaded nanoparticles targeted to the site of infection enhance antibacterial efficacy.

Bacterial resistance to antibiotics has made it necessary to resort to antibiotics that have considerable toxicities. Here, we show that the cyclic 9-amino acid peptide CARGGLKSC (CARG), identified via phage display on () bacteria and through screening in mice with -induced lung infections, increases the antibacterial activity of CARG-conjugated vancomycin-loaded nanoparticles in -infected tissues and reduces the needed overall systemic dose, minimizing side effects. CARG binds specifically to bacteria but not Pseudomonas bacteria , selectively accumulates in -infected lungs and skin of mice but not in non-infected tissue and Pseudomonas-infected tissue, and significantly enhances the accumulation of intravenously injected vancomycin-loaded porous silicon nanoparticles bearing the peptide in -infected mouse lung tissue. The targeted nanoparticles more effectively suppress staphylococcal infections relative to equivalent doses of untargeted vancomycin nanoparticles or of free vancomycin. The therapeutic delivery of antibiotic-carrying nanoparticles bearing peptides targeting infected tissue may help combat difficult-to-treat infections.