title: Membrane interactions of mesoporous silica nanoparticles as carriers of antimicrobial peptides.
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 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.
authors.affiliation: Department of Inorganic Chemistry 2, University of Ulm, D-89031 Ulm, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Braun
authors.affiliation: Department of Inorganic Chemistry 2, University of Ulm, D-89031 Ulm, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pochert
authors.affiliation: Department of Inorganic Chemistry 2, University of Ulm, D-89031 Ulm, Germany. Electronic address: mika.linden@uni-ulm.de.
authors.forename: Mika
authors.initials: M
authors.lastname: Lindén
authors.affiliation: Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-221 84 Lund, Sweden.
authors.forename: Mina
authors.initials: M
authors.lastname: Davoudi
authors.affiliation: Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-221 84 Lund, Sweden; Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore 308232, Singapore.
authors.forename: Artur
authors.initials: A
authors.lastname: Schmidtchen
authors.affiliation: Department of Pharmacy, Uppsala University, SE-75123 Uppsala, Sweden.
authors.forename: Randi
authors.initials: R
authors.lastname: Nordström
authors.affiliation: Department of Pharmacy, Uppsala University, SE-75123 Uppsala, Sweden. Electronic address: martin.malmsten@farmaci.uu.se.
authors.forename: Martin
authors.initials: M
authors.lastname: Malmsten
mesh_terms: D000327:Adsorption; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D012822:Silicon Dioxide
keywords: Antimicrobial peptide; Drug delivery; Membrane; Mesoporous silica