TY - JOUR

T1 - Membrane interactions of mesoporous silica nanoparticles as carriers of antimicrobial peptides

AU - Braun, Katharina

AU - Pochert, Alexander

AU - Lindén, Mika

AU - Davoudi, Mina

AU - Schmidtchen, Artur

AU - Nordström, Randi

AU - Malmsten, Martin

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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.

AB - 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.

KW - Adsorption

KW - Anti-Bacterial Agents

KW - Cell Survival

KW - Drug Carriers

KW - Erythrocytes

KW - Escherichia coli

KW - Humans

KW - Microbial Sensitivity Tests

KW - Nanoparticles

KW - Particle Size

KW - Porosity

KW - Silicon Dioxide

KW - Surface Properties

KW - Journal Article

U2 - 10.1016/j.jcis.2016.05.002

DO - 10.1016/j.jcis.2016.05.002

M3 - Journal article

C2 - 27174622

VL - 475

SP - 161

EP - 170

JO - Journal of Colloid and Interface Science

JF - Journal of Colloid and Interface Science

SN - 0021-9797

ER -