Nanoparticles and antigen-specific T-cell therapeutics: a comprehensive study on uptake and release

• Published in: Nanomedicine (London, England) Vol. 10; no. 7; pp. 1063 - 1076
• Main Authors: Zupke, Oliver, Distler, Eva, Jürchott, Anna, Paiphansiri, Umaporn, Dass, Martin, Thomas, Simone, Hartwig, Udo F, Theobald, Matthias, Landfester, Katharina, Mailänder, Volker, Herr, Wolfgang
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.04.2015
• Subjects: Analysis; Animals; Autoimmune diseases; Care and treatment; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - metabolism; cell imaging; Cell Line; cellular therapy; Diagnosis; Drug Carriers - chemistry; Drug Carriers - metabolism; drug delivery; Drug Delivery Systems; Drug Liberation; Endocytosis; Health aspects; Humans; Immune response; leukemia; Magnetic resonance imaging; Mice, Inbred C57BL; Microscopy, Confocal; Microscopy, Electron, Transmission; nanoparticles; Nanoparticles - chemistry; Nanoparticles - metabolism; Nanoparticles - ultrastructure; NP release; Polymers - chemistry; Polymers - metabolism; T cells; T lymphocytes; tumor; NP release; T lymphocytes; leukemia; nanoparticles; tumor; cell imaging; endocytosis; drug delivery; cellular therapy
• ISSN: 1743-5889; 1748-6963
• DOI: 10.2217/nnm.14.160

T lymphocytes are used as cellular therapeutics in many disease entities including cancer. We investigated the uptake and retention of nanoparticles (NPs) by these nonphagocytic cells. Uptake, release and toxicity of various polymeric NP preparations were analyzed by flow cytometry, confocal laser scanning microscopy and transmission electron microscopy. T-cell effector functions were measured using IFN-γ-ELISPOT and Chromium-release assays. Amino-functionalized NPs were efficiently ingested by antigen-specific T cells without adversely influencing effector functions. NPs were stored in membrane-surrounded vesicles, with major proportions released extracellularly during 24 h. Amino-functionalized polymeric NPs are efficiently taken up by human T cells and could be used to design nanocarriers for direct access and manipulation of antigen-specific T cells .