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Interleukin-2 Functionalized Nanocapsules for T Cell-Based Immunotherapy

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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
Cite this: ACS Nano 2016, 10, 10, 9216–9226
Publication Date (Web):October 10, 2016
Copyright © 2016 American Chemical Society

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    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.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsnano.5b07973.

    • Synthesis and functionalization of HES nanocapsules; Synthesis of 9-(azidomethyl)anthracene (anth-N3); In Vivo application of nanocapsules. Figure S1a: IL-2 functionalization of HES nanocapsules in a multistep process: miniemulsion. Figure S1b: IL-2 functionalization of HES nanocapsules in a multistep process. Figure S1c: IL-2 functionalization of HES nanocapsules in a multistep process: MALDI-TOF. Figure S1d: IL-2 functionalization of HES nanocapsules in a multistep process: HPLC. Figure S2: Biological activity of IL-2 on IL-2-dependent murine CTLL-2 cells. Figure S3: Nanocapsule uptake by human CD4+CD25high T cells. Figure S4: Human CD4+CD25high T cell proliferation induced by HES-D-IL-2. Figure S5: Nanocapsule-induced cytotoxicity. Figure S6: Basiliximab did not affect the uptake of control HES-D nanocapsules in human CD4+CD25+ T cells. Figure S7: HES-D-IL-2, HES-D-IL-2/2, and HES-D-IL-2/10-induced CTLL-2 proliferation. Figure S8: Phenotype and uptake of human naïve CD4+CD25, activated effector CD4+CD25+, and regulatory CD4+ CD25high T cell populations. Figure S9: Uptake of HES-D-IL-2, HES-D-IL-2/2, and HES-D-IL-2/10 nanocapsules by human naïve CD4+CD25, activated CD4+CD25+, and regulatory CD4+CD25high T cells. Figure S10: In vivo uptake of HES-D-IL-2 nanocapsules (PDF)

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