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

Karawacka, Weronika, Janko, Christina, Unterweger, Harald, Mühlberger, Marina, Lyer, Stefan, Taccardi, Nicola, Mokhir, Andriy, Jira, Wolfgang, Peukert, Wolfgang, Boccaccini, Aldo R., Kolot, Mikhail, Strauss, Richard, Bogdan, Christian, Alexiou, Christoph, Tietze, Rainer
Colloids and surfaces 2019 v.174 pp. 95-102
acute course, biocompatibility, colloids, humans, inflammation, iron oxides, lipopolysaccharides, magnetism, nanoparticles, pathogens, peptides, proteins, sepsis (infection), thiols
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.