Interleukin-2 Functionalized Nanocapsules for T Cell-Based lmmunotherapy

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 nanocapsulemediated technique is a promising strategy for T cell-based immunotherapies and may be translated to other cytokinerelated targeting systems.