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

• Published in: Biomaterials Vol. 34; no. 38; pp. 10249 - 10257
• Main Authors: Hajdu, Péter, Chimote, Ameet A, Thompson, Tyler H, Koo, Youngmi, Yun, Yeoheung, Conforti, Laura
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-12-2013
• 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; Autoimmunity; Kv1.3 ion channel; siRNA; T cell; Lipid nanoparticles
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.09.019

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.