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

TitleAntibiotic-loaded nanoparticles targeted to the site of infection enhance antibacterial efficacy.
Publication TypeJournal Article
Year of Publication2018
AuthorsHussain S, Joo J, Kang J, Kim B, Braun GB, She Z-G, Kim D, Mann AP, Mölder T, Teesalu T, Carnazza S, Guglielmino S, Sailor MJ, Ruoslahti E
JournalNat Biomed Eng
Volume2
Issue2
Pagination95-103
Date Published2018 Feb
ISSN2157-846X
Abstract

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.

DOI10.1038/s41551-017-0187-5
Alternate JournalNat Biomed Eng
PubMed ID29955439
PubMed Central IDPMC6015743
Grant ListP30 CA030199 / CA / NCI NIH HHS / United States
R01 AI132413 / AI / NIAID NIH HHS / United States