Functionalized liposomes loaded with siRNAs targeting ion channels in effector memory T cells as a potential therapy for autoimmunity.
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 Ca(2+) 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 Ca(2+) influx. Our results can form the basis of an innovative therapeutic approach in autoimmunity.
University of Cincinnati, Department of Internal Medicine, Division of Nephrology and Hypertension, 231 Albert Sabin Way, Cincinnati, OH 45267-0585, USA.
Péter
P
Hajdu
Ameet A
AA
Chimote
Tyler H
TH
Thompson
Youngmi
Y
Koo
Yeoheung
Y
Yun
Laura
L
Conforti
D015551:Autoimmunity / Q000276:immunology*; D002478:Cells, Cultured; D004594:Electrophysiology; D006801:Humans; D007150:Immunohistochemistry; D008081:Liposomes / Q000737:chemistry*; D018613:Microscopy, Confocal; D034741:RNA, Small Interfering / Q000737:chemistry*; D013601:T-Lymphocytes / Q000276:immunology*
D008081:Liposomes; D034741:RNA, Small Interfering
Autoimmunity; Kv1.3 ion channel; Lipid nanoparticles; T cell; siRNA