Functionalized liposomes loaded with siRNAs targeting ion channels in effector memory T cells as a potential therapy for autoimmunity

Abstract Effector memory T cells (TM ) play a key role in the pathology of certain autoimmune disorders. The activity of effector TM cells is under the control of Kv1.3 ion channels, which facilitate the Ca2+ influx necessary for T cell activation and function, i.e. cytokine release and proliferatio...

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Bibliographic Details
Published in:Biomaterials 2013-12, Vol.34 (38), p.10249-10257
Main Authors: Hajdu, Péter, Chimote, Ameet A, Thompson, Tyler H, Koo, Youngmi, Yun, Yeoheung, Conforti, Laura
Format: Article
Language:English
Subjects:
Advanced Basic Science
Autoimmunity
Autoimmunity - immunology
Cells, Cultured
Dentistry
Electrophysiology
Humans
Immunohistochemistry
Kv1.3 ion channel
Lipid nanoparticles
Liposomes - chemistry
Microscopy, Confocal
RNA, Small Interfering - chemistry
siRNA
T cell
T-Lymphocytes - immunology
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Summary:Abstract Effector memory T cells (TM ) play a key role in the pathology of certain autoimmune disorders. The activity of effector TM cells is under the control of Kv1.3 ion channels, which facilitate the Ca2+ influx necessary for T cell activation and function, i.e. cytokine release and proliferation. Consequently, the knock-down of Kv1.3 expression in effector TM 's may be utilized as a therapy for the treatment of autoimmune diseases. In this study we synthesized lipid unilamellar nanoparticles (NPs) that can selectively deliver Kv1.3 siRNAs into TM cells in vitro . NPs made from a mixture of phosphatidylcholine, pegylated/biotinylated phosphoethanolamine and cholesterol were functionalized with biotinylated-CD45RO (cell surface marker of TM 's) antibodies via fluorophore-conjugated streptavidin (CD45RO-NPs). Incubation of T cells with CD45RO-NPs resulted into the selective attachment and endocytosis of the NPs into TM 's. Furthermore, the siRNA against Kv1.3, encapsulated into the CD45RO-NPs, was released into the cytosol. Consequently, the expression of Kv1.3 channels decreased significantly in TM 's, which led to a remarkable decrease in Ca2+ influx. Our results can form the basis of an innovative therapeutic approach in autoimmunity.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2013.09.019