SPIONs functionalized with small peptides for binding of lipopolysaccharide, a pathophysiologically relevant microbial product.

Weronika Karawacka, Christina Janko, Harald Unterweger, Marina Mühlberger, Stefan Lyer, Nicola Taccardi, Andriy Mokhir, Wolfgang Jira, Wolfgang Peukert, Aldo R Boccaccini, Mikhail Kolot, Richard Strauss, Christian Bogdan, Christoph Alexiou, Rainer Tietze

Journal: Colloids and surfaces. B, Biointerfaces 2019;174():95-102

PMID: 30445255

Full Text on Elsevier Science View on PubMed

Abstract

Systemic inflammation such as sepsis represents an acute life-threatening condition, to which often no timely remedy can be found. A promising strategy may be to functionalize magnetic nanoparticles with specific peptides, derived from the binding motives of agglutinating salivary proteins, that allow immobilization of pathogens. In this work, superparamagnetic iron oxide nanoparticles with stable polycondensed aminoalkylsilane layer were developed, to which the heterobifunctional linkers N-succinimidyl 3-(2-pyridyldithio)-propanoate (SDPD) and N-succinimidyl bromoacetate (SBA) were bound. These linkers were further chemoselectively reacted with the thiol group of singularly present cysteines of selected peptides. The resulting functional nanoparticles underwent a detailed physicochemical characterization. The biocompatibility of the primarily coated aminoalkylsilane particles was also investigated. To test the pathogen-binding efficacy of the particles, the lipopolysaccharide-immobilization capacity of the peptide-coated particles was compared with free peptides. Here, one particle-bound peptide species succeeded in capturing 90% of the toxin, whereas the degree of immobilization of the toxin with a system that varied in the sequence of the peptide dropped to 35%. With these promising results, we hope to develop extracorporeal magnetic clearance systems for removing pathogens from the human body in order to accelerate diagnosis and alleviate acute disease conditions such as sepsis.

Address: Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, Universitätsklinikum Erlangen, 91054 Erlangen, Germany.; Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, Universitätsklinikum Erlangen, 91054 Erlangen, Germany. Electronic address: [email protected].; Institute of Chemical Reaction Engineering, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, 91058 Erlangen, Germany.; Department of Chemistry and Pharmacy, Organic Chemistry Chair II, FAU 91058 Erlangen, Germany.; Federal Research Institute of Nutrition and Food, Max Rubner-Institut, 95326 Kulmbach, Germany.; Institute of Particle Technology (LFG), FAU, 91058 Erlangen, Germany; Interdisciplinary Center for Functional Particle Systems (FPS), FAU, 91058 Erlangen, Germany.; Interdisciplinary Center for Functional Particle Systems (FPS), FAU, 91058 Erlangen, Germany; Institute of Biomaterials, Department of Materials Science and Engineering, FAU, 91058 Erlangen, Germany.; Department of Biochemistry and Molecular Biology, Tel-Aviv University, Tel-Aviv 69978, Israel.; Deptartment of Medicine 1, Universitätsklinikum Erlangen, 91054 Erlangen, Germany.; Institut für Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, 91054 Erlangen, Germany; Medical Immunology Campus Erlangen, FAU Erlangen-Nürnberg, 91054 Erlangen, Germany.

DOI: 10.1016/j.colsurfb.2018.11.002

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MeSH Terms: Endotoxins, Ferric Compounds, Humans, Jurkat Cells, Lipopolysaccharides, Magnetite Nanoparticles, Peptide Fragments