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Antibiotic-loaded nanoparticles targeted to the site of infection enhance antibacterial efficacy
Open accessAbstract
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 Staphylococcus aureus (S. aureus) bacteria and through in vivo screening in mice with S. aureus-induced lung infections, increases the antibacterial activity of CARG-conjugated vancomycin-loaded nanoparticles in S. aureus-infected tissues and reduces the needed overall systemic dose, minimizing side effects. CARG binds specifically to S. aureus bacteria but not Pseudomonas bacteria in vitro, selectively accumulates in S. aureus-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 S. aureus-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 tissue may help combat difficult-to-treat infections.
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“In a 20 day efficacy study, 100% of the mice administered the peptide-functionalized nanoparticles survived, compared with roughly 40% survival in the non-functionalized-nanoparticle and free-vancomycin cohorts.”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [56]
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Metadata
- Authors
- Hussain, S., Joo, J., Kang, J., Kim, B., Braun, G. B., She, Z.-G., Kim, D., Mann, A. P., Mölder, T., Teesalu, T., Carnazza, S., Guglielmino, S., Sailor, M. J., & Ruoslahti, E.
- Affiliations
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Asan Medical Center (KR)
- University of California San Diego (US)
- University of Tartu (EE)
- University of California, Santa Barbara (US)
- University of Messina (IT)
- Corresponding author
- Ruoslahti, Erkki
- ORCID
- Venue
- Nature Biomedical Engineering
- Published
- 2018-01-22
- Volume
- 2
- Issue
- 2
- Pages
- 95-103
- ISSN
- 2157-846X (ISSN-L)
- PMC
- PMC6015743
- OpenAlex
- W2789337312
- Cited by
- 399
- References
- 61
- Citations by year
- 2026: 26 · 2025: 48 · 2024: 56 · 2023: 52 · 2022: 53 · 2021: 53 · 2020: 61 · 2019: 34 · 2018: 15
- FWCI
- 13.20
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- Locations
- Nature Biomedical Engineering (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Scholarworks@UNIST (Ulsan National Institute of Science and Technology) (submittedVersion)
- Funders
- National Cancer Institute (P30CA030199)
- National Institute of Allergy and Infectious Diseases (R01AI132413)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Pharmacology (medical) › Antibiotics Pharmacokinetics and Efficacy
- Keywords
- antibiotic-loaded nanoparticles, vancomycin, targeted drug delivery, Staphylococcus aureus, phage display, porous silicon nanoparticles, bacterial infection, pulmonary infection, skin infections, antibiotic resistance, Pseudomonas
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