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

Tenland, Erik LU ; Pochert, Alexander; Krishnan, Nitya; Rao, Komal Umashankar LU ; Kalsum, Sadaf; Braun, Katharina; Glegola-Madejska, Izabela; Lerm, Maria; Robertson, Brian D. and Lindén, Mika, et al. (2019) In PLoS ONE 14(2).
Abstract

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... (More)

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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PLoS ONE
volume
14
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2
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Public Library of Science
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  • scopus:85062069519
ISSN
1932-6203
DOI
10.1371/journal.pone.0212858
language
English
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yes
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89f30954-7f23-4324-914a-74d1a025d877
date added to LUP
2019-03-06 13:10:56
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2019-04-02 04:14:28
@article{89f30954-7f23-4324-914a-74d1a025d877,
  abstract     = {<p>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.</p>},
  articleno    = {e0212858},
  author       = {Tenland, Erik and Pochert, Alexander and Krishnan, Nitya and Rao, Komal Umashankar and Kalsum, Sadaf and Braun, Katharina and Glegola-Madejska, Izabela and Lerm, Maria and Robertson, Brian D. and Lindén, Mika and Godaly, Gabriela},
  issn         = {1932-6203},
  language     = {eng},
  month        = {02},
  number       = {2},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Effective delivery of the anti-mycobacterial peptide NZX in mesoporous silica nanoparticles},
  url          = {http://dx.doi.org/10.1371/journal.pone.0212858},
  volume       = {14},
  year         = {2019},
}