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

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

Carnazza, Santina;Guglielmino, Salvatore;
2018-01-01

Abstract

Bacterial resistance to antibiotics has made it necessary to resort to using antibacterial drugs that have considerable toxicities. Here, we show that conjugation of vancomycin-loaded nanoparticles with the cyclic 9-amino-acid peptide CARGGLKSC (CARG), identified via phage display on Stophylococcus oureus (S. oureus) bacteria and through in vivo screening in mice with S. oureusinduced lung infections, increases the antibacterial activity of the nanoparticles in S. oureus-infected tissues and reduces the systemic dose needed, minimizing side effects. CARG binds specifically to S. oureus bacteria but not Pseudomonos bacteria in vitro, selectively accumulates in S. oureus-intected lungs and skin of mice but not in non-infected tissue and Pseudomonosintected tissue, and significantly enhances the accumulation of intravenously injected vancomycin-loaded porous silicon nanoparticles bearing CARG in S. oureus-infected mouse lung tissue. The targeted nanoparticles more effectively suppress staphylococcal infections in vivo relative to equivalent doses of untargeted vancomycin nanoparticles or of free vancomycin. The therapeutic delivery of antibiotic-carrying nanoparticles bearing peptides targeting infected tissues may help combat difficult- to-treat infections.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3121340
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