title: Tumor necrosis factor (TNF)-functionalized nanostructured particles for the stimulation of membrane TNF-specific cell responses.
abstract: Most members of the tumor necrosis factor (TNF) ligand family occur in both a membrane-bound and a soluble form, which can possess differential bioactivities. The aim of this work was the construction of a synthetic-biological hybrid system consisting of chemically nanostructured core-shell particles with a diameter of 100 nm, 1 microm, or 10 microm and the cytokine TNF to obtain a tool that mimics the bioactivity of naturally occurring membrane-bound TNF. Synthetic core-shell nanoparticles consisting of an inorganic silica core and an ultrathin organic shell bearing a maleimide group at the shell surface which allowed for a covalent and site-directed coupling of CysHisTNF mutants were prepared. The TNF mutants were modified at the N-terminus by PCR cloning by introducing a His-Tag for purification and a free cysteine group for reaction with the particle-attached maleimide group. The resulting nanostructured hybrid particles initiated strong TNF receptor type 2 specific responses, otherwise only seen for the membrane-bound form of TNF, but not the soluble cytokine, thus clearly demonstrating new and membrane TNF-like properties of the bioconjugated soluble TNF.
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, D-70569 Stuttgart, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Bryde
authors.forename: Ingo
authors.initials: I
authors.lastname: Grunwald
authors.forename: Angela
authors.initials: A
authors.lastname: Hammer
authors.forename: Anja
authors.initials: A
authors.lastname: Krippner-Heidenreich
authors.forename: Thomas
authors.initials: T
authors.lastname: Schiestel
authors.forename: Herwig
authors.initials: H
authors.lastname: Brunner
authors.forename: Günter E M
authors.initials: GE
authors.lastname: Tovar
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfizenmaier
authors.forename: Peter
authors.initials: P
authors.lastname: Scheurich
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008301:Maleimides; D008565:Membrane Proteins / Q000737:chemistry; D051379:Mice; D018716:Molecular Mimicry; D009154:Mutation; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism*; D012822:Silicon Dioxide; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry* / Q000235:genetics
chemical_list: D008024:Ligands; D008301:Maleimides; D008565:Membrane Proteins; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; C043592:maleimide; D012822:Silicon Dioxide