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  • Tenland, ErikLund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,Lund Univ, Sweden (author)

Effective delivery of the anti-mycobacterial peptide NZX in mesoporous silica nanoparticles

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-02-26
  • PUBLIC LIBRARY SCIENCE,2019
  • electronicrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:liu-155571
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-155571URI
  • https://doi.org/10.1371/journal.pone.0212858DOI
  • https://lup.lub.lu.se/record/89f30954-7f23-4324-914a-74d1a025d877URI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agencies|European Unions Seventh Framework Programme (FP7/2007-2013) [604182]; DFG [SFB 1279]; UK Medical Research Council; Swedish Heart-Lung Foundation [20150733]; Alfred Osterlunds Foundation; Royal Physiographic Society of Lund
  • Background Intracellular delivery of antimicrobial agents by nanoparticles, such as mesoporous silica particles (MSPs), offers an interesting strategy to treat intracellular infections. In tuberculosis (TB), Mycobacterium tuberculosis avoids components of the immune system by residing primarily inside alveolar macrophages, which are the desired target for TB therapy. Methods and findings We have previously identified a peptide, called NZX, capable of inhibiting both clinical and multi-drug resistant strains of M. tuberculosis at therapeutic concentrations. In this study we analysed the potential of MSPs containing NZX for the treatment of tuberculosis. The MSPs released functional NZX gradually into simulated lung fluid and the peptide filled MSPs were easily taken up by primary macrophages. In an intracellular infection model, the peptide containing particles showed increased mycobacterial killing compared to free peptide. The therapeutic potential of peptide containing MSPs was investigated in a murine infection model, showing that MSPs preserved the effect to eliminate M. tuberculosis in vivo. Conclusions In this study we found that loading the antimicrobial peptide NZX into MSPs increased the inhibition of intracellular mycobacteria in primary macrophages and preserved the ability to eliminate M. tuberculosis in vivo in a murine model. Our studies provide evidence for the feasibility of using MSPs for treatment of tuberculosis.

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  • Pochert, AlexanderUlm Univ, Germany,University of Ulm (author)
  • Krishnan, NityaImperial Coll London, England,Imperial College London (author)
  • Rao, Komal UmashankarLund University,Lunds universitet,Medicinsk mikrobiologi,Forskargrupper vid Lunds universitet,Medical Microbiology,Lund University Research Groups,Lund Univ, Sweden(Swepub:lu)ko3044um (author)
  • Kalsum, SadafLinköping University,Linköpings universitet,Medicinska fakulteten,Avdelningen för mikrobiologi, infektion och inflammation(Swepub:liu)sadka44 (author)
  • Braun, KatharinaLund Univ, Sweden,Lund University (author)
  • Glegola-Madejska, IzabelaImperial Coll London, England,Imperial College London (author)
  • Lerm, MariaLinköping University,Linköpings universitet,Medicinska fakulteten,Avdelningen för mikrobiologi, infektion och inflammation(Swepub:liu)marle69 (author)
  • Robertson, Brian D.Imperial Coll London, England,Imperial College London (author)
  • Linden, MikaUlm Univ, Germany,University of Ulm (author)
  • Godaly, GabrielaLund University,Lunds universitet,Medicinsk mikrobiologi,Forskargrupper vid Lunds universitet,Medical Microbiology,Lund University Research Groups,Lund Univ, Sweden(Swepub:lu)mmb-ggo (author)
  • Avdelningen för mikrobiologi, immunologi och glykobiologi - MIGInstitutionen för laboratoriemedicin (creator_code:org_t)

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  • In:PLOS ONE: PUBLIC LIBRARY SCIENCE14:21932-6203

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