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Membrane interactions of mesoporous silica nanoparticles as carriers of antimicrobial peptides

Braun, Katharina; Pochert, Alexander; Lindén, Mika; Davoudi, Mina LU ; Schmidtchen, Artur LU ; Nordström, Randi and Malmsten, Martin (2016) In Journal of Colloid and Interface Science 475. p.161-170
Abstract

Membrane interactions are critical for the successful use of mesoporous silica nanoparticles as delivery systems for antimicrobial peptides (AMPs). In order to elucidate these, we here investigate effects of nanoparticle charge and porosity on AMP loading and release, as well as consequences of this for membrane interactions and antimicrobial effects. Anionic mesoporous silica particles were found to incorporate considerable amounts of the cationic AMP LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES (LL-37), whereas loading is much lower for non-porous or positively charged silica nanoparticles. Due to preferential pore localization, anionic mesoporous particles, but not the other particles, protect LL-37 from degradation by infection-related... (More)

Membrane interactions are critical for the successful use of mesoporous silica nanoparticles as delivery systems for antimicrobial peptides (AMPs). In order to elucidate these, we here investigate effects of nanoparticle charge and porosity on AMP loading and release, as well as consequences of this for membrane interactions and antimicrobial effects. Anionic mesoporous silica particles were found to incorporate considerable amounts of the cationic AMP LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES (LL-37), whereas loading is much lower for non-porous or positively charged silica nanoparticles. Due to preferential pore localization, anionic mesoporous particles, but not the other particles, protect LL-37 from degradation by infection-related proteases. For anionic mesoporous nanoparticles, membrane disruption is mediated almost exclusively by peptide release. In contrast, non-porous silica particles build up a resilient LL-37 surface coating due to their higher negative surface charge, and display largely particle-mediated membrane interactions and antimicrobial effects. For positively charged mesoporous silica nanoparticles, LL-37 incorporation promotes the membrane binding and disruption displayed by the particles in the absence of peptide, but also causes toxicity against human erythrocytes. Thus, the use of mesoporous silica nanoparticles as AMP delivery systems requires consideration of membrane interactions and selectivity of both free peptide and the peptide-loaded nanoparticles, the latter critically dependent on nanoparticle properties.

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organization
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type
Contribution to journal
publication status
published
subject
keywords
Antimicrobial peptide, Drug delivery, Membrane, Mesoporous silica
in
Journal of Colloid and Interface Science
volume
475
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:84965158302
  • wos:000376708400019
ISSN
0021-9797
DOI
10.1016/j.jcis.2016.05.002
language
English
LU publication?
yes
id
332deda9-fca0-4c57-9fe6-0874f176029f
date added to LUP
2016-09-27 11:06:37
date last changed
2017-05-02 13:14:51
@article{332deda9-fca0-4c57-9fe6-0874f176029f,
  abstract     = {<p>Membrane interactions are critical for the successful use of mesoporous silica nanoparticles as delivery systems for antimicrobial peptides (AMPs). In order to elucidate these, we here investigate effects of nanoparticle charge and porosity on AMP loading and release, as well as consequences of this for membrane interactions and antimicrobial effects. Anionic mesoporous silica particles were found to incorporate considerable amounts of the cationic AMP LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES (LL-37), whereas loading is much lower for non-porous or positively charged silica nanoparticles. Due to preferential pore localization, anionic mesoporous particles, but not the other particles, protect LL-37 from degradation by infection-related proteases. For anionic mesoporous nanoparticles, membrane disruption is mediated almost exclusively by peptide release. In contrast, non-porous silica particles build up a resilient LL-37 surface coating due to their higher negative surface charge, and display largely particle-mediated membrane interactions and antimicrobial effects. For positively charged mesoporous silica nanoparticles, LL-37 incorporation promotes the membrane binding and disruption displayed by the particles in the absence of peptide, but also causes toxicity against human erythrocytes. Thus, the use of mesoporous silica nanoparticles as AMP delivery systems requires consideration of membrane interactions and selectivity of both free peptide and the peptide-loaded nanoparticles, the latter critically dependent on nanoparticle properties.</p>},
  author       = {Braun, Katharina and Pochert, Alexander and Lindén, Mika and Davoudi, Mina and Schmidtchen, Artur and Nordström, Randi and Malmsten, Martin},
  issn         = {0021-9797},
  keyword      = {Antimicrobial peptide,Drug delivery,Membrane,Mesoporous silica},
  language     = {eng},
  month        = {08},
  pages        = {161--170},
  publisher    = {Elsevier},
  series       = {Journal of Colloid and Interface Science},
  title        = {Membrane interactions of mesoporous silica nanoparticles as carriers of antimicrobial peptides},
  url          = {http://dx.doi.org/10.1016/j.jcis.2016.05.002},
  volume       = {475},
  year         = {2016},
}