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

Autor: Hussain S; Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA., Joo J; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.; Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.; Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea., Kang J; Department of Nanoengineering, University of California, San Diego, La Jolla, CA, USA., Kim B; Materials Science and Engineering Program, University of California, San Diego, La Jolla, CA, USA., Braun GB; Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.; STEMCELL Technologies Inc., Vancouver, Canada., She ZG; Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China., Kim D; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA., Mann AP; Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA., Mölder T; Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia., Teesalu T; Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.; Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.; Center for Nanomedicine, and Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA., Carnazza S; Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali- ChiBioFarAm, Università di Messina, Messina, Italy., Guglielmino S; Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali- ChiBioFarAm, Università di Messina, Messina, Italy., Sailor MJ; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.; Department of Nanoengineering, University of California, San Diego, La Jolla, CA, USA.; Materials Science and Engineering Program, University of California, San Diego, La Jolla, CA, USA., Ruoslahti E; Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. ruoslahti@sbpdiscovery.org.; Center for Nanomedicine, and Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA. ruoslahti@sbpdiscovery.org.
Jazyk: angličtina
Zdroj: Nature biomedical engineering [Nat Biomed Eng] 2018 Feb; Vol. 2 (2), pp. 95-103. Date of Electronic Publication: 2018 Jan 22.
DOI: 10.1038/s41551-017-0187-5
Abstrakt: 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.
Competing Interests: Competing financial interests M.J.S is a scientific founder of Spinnaker Biosciences, Inc., and has an equity interest in the company. Although the R01 AI132413-01 grant has been identified for conflict of interest management based on the overall scope of the project and its potential benefit to Spinnaker Biosciences, Inc., the research findings included in this particular publication may not necessarily relate to the interests of Spinnaker Biosciences, Inc. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. All the other authors declare no competing financial interests.
Databáze: MEDLINE
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