title: Interleukin-2 Functionalized Nanocapsules for T Cell-Based Immunotherapy.
abstract: A major demand on immunotherapy is the direct interference with specific immune cells in vivo. In contrast to antibody-engineered nanoparticles to control dendritic cells function, targeting of T cells for biomedical applications still remains an obstacle as they disclose reduced endocytic activities. Here, by coupling the cytokine interleukin-2 (IL-2) to the surface of hydroxyethyl starch nanocapsules, we demonstrated a direct and specifc T cell targeting in vitro and in vivo by IL-2 receptor-mediated internalization. For this purpose, defined amounts of azide-functionalized IL-2 were linked to alkyne-functionalized hydroxyethyl starch nanocapsules via copper-free click reactions. In combination with validated quantification of the surface-linked IL-2 with anthracen azide, this method allowed for engineering IL-2-functionalized nanocapsules for an efficient targeting of human and murine T cell populations with various IL-2 receptor affinities. This nanocapsule-mediated technique is a promising strategy for T cell-based immunotherapies and may be translated to other cytokine-related targeting systems.
authors.affiliation: Department of Dermatology, University Medical Center Mainz, Johannes Gutenberg-University Mainz , Mainz D-55099, Germany.
authors.forename: Stefanie U
authors.initials: SU
authors.lastname: Frick
authors.affiliation: Department of Dermatology, University Medical Center Mainz, Johannes Gutenberg-University Mainz , Mainz D-55099, Germany.|Max Planck Institute for Polymer Research , Mainz D-55128, Germany.
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Domogalla
authors.affiliation: Max Planck Institute for Polymer Research , Mainz D-55128, Germany.
authors.forename: Grit
authors.initials: G
authors.lastname: Baier
authors.affiliation: Max Planck Institute for Polymer Research , Mainz D-55128, Germany.
authors.forename: Frederik R
authors.initials: FR
authors.lastname: Wurm
authors.affiliation: Department of Dermatology, University Medical Center Mainz, Johannes Gutenberg-University Mainz , Mainz D-55099, Germany.|Max Planck Institute for Polymer Research , Mainz D-55128, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Mailänder
authors.affiliation: Max Planck Institute for Polymer Research , Mainz D-55128, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Landfester
authors.affiliation: Department of Dermatology, University Medical Center Mainz, Johannes Gutenberg-University Mainz , Mainz D-55099, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Steinbrink
keywords: T cells; click chemistry; human; hydroxyethyl starch; immunotherapy; interleukin-2; murine; nanocapsules