Membrane interactions of mesoporous silica nanoparticles as carriers of antimicrobial peptides

• Published in: Journal of colloid and interface science Vol. 475; pp. 161 - 170
• Main Authors: Braun, Katharina, Pochert, Alexander, Lindén, Mika, Davoudi, Mina, Schmidtchen, Artur, Nordström, Randi, Malmsten, Martin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2016
• Subjects: Adsorption; Andra medicinska och farmaceutiska grundvetenskaper; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacology; Antiinfectives and antibacterials; Antimicrobial peptide; Basic Medicine; Cell Survival - drug effects; Charged particles; Delivery systems; Disruption; Drug Carriers - chemistry; Drug delivery; Erythrocytes - drug effects; Escherichia coli - drug effects; Humans; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Membrane; Membranes; Mesoporous silica; Microbial Sensitivity Tests; Nanoparticles; Nanoparticles - chemistry; Other Basic Medicine; Particle Size; Peptides; Porosity; Silicon dioxide; Silicon Dioxide - chemistry; Surface Properties; Membrane; Drug delivery; Mesoporous silica; Antimicrobial peptide
• ISSN: 0021-9797; 1095-7103; 1095-7103
• DOI: 10.1016/j.jcis.2016.05.002

[Display omitted] 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.