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


METHODS
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 (51)Chromium-release assays.


RESULTS
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.


CONCLUSIONS
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 in vivo.
Department of Medicine III, Hematology, Oncology & Pneumology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
Oliver
O
Zupke
Eva
E
Distler
Anna
A
Jürchott
Umaporn
U
Paiphansiri
Martin
M
Dass
Simone
S
Thomas
Udo F
UF
Hartwig
Matthias
M
Theobald
Katharina
K
Landfester
Volker
V
Mailänder
Wolfgang
W
Herr
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004705:Endocytosis; D006801:Humans; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*
D004337:Drug Carriers; D011108:Polymers
NP release; T lymphocytes; cell imaging; cellular therapy; drug delivery; endocytosis; leukemia; nanoparticles; tumor