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TNF-Funtionalized nanostructured particles for the stimulation of Membrane TNF-specific Cell responses

Lookup NU author(s): Dr Anja Krippner-Heidenreich

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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.

Publication metadata

Author(s): Bryde S, Grunwald I, Hammer A, Krippner-Heidenreich A, Schiestel T, Brunner H, Tovar GEM, Pfizenmaier K, Scheurich P

Publication type: Article

Publication status: Published

Journal: Bioconjugate Chemistry

Year: 2005

Volume: 16

Issue: 6

Pages: 1459-1467

ISSN (print): 1043-1802

ISSN (electronic): 1520-4812

Publisher: American Chemical Society

URL: http://dx.doi.org/10.1021/bc0501810

DOI: 10.1021/bc0501810

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