Abstract
Hyperactive effector memory T cells (TEM) play a key role in cardiovascular complications of the autoimmune disease systemic lupus erythematosus (SLE). SLE TEM's have higher intracellular Ca2+ level, which contributes to their hyperactivity. Kv1.3 channels facilitate Ca2+ influx in T cells. Therefore silencing the Kv1.3 gene selectively in TEM's can be used as novel immunosuppressive therapy. Here we demonstrate that lipid nanoparticles (NPs) can be used to selectively deliver Kv1.3 siRNAs into TEM cells. Specificity and efficacy of Kv1.3 siRNAs was determined by RT‐qPCR and electrophysiology. NPs were made from a mixture of phosphatidylcholine, phosphoethanolamine‐PEG2000‐biotin and cholesterol. NPs were functionalized with inactive biotin‐CD45RO (TEM marker) antibodies via fluorophore‐conjugated streptavidin. Human T and MOLT‐4 (TEM cell line) cells were used to test the specific binding of NPs to TEM cells. NPs (ca. 100 nm) were characterized by dynamic light scattering and fluorescent/electron microscopy. Incubation of T/MOLT‐4 cells with CD45RO‐coated NPs resulted into the selective attachment and endocytosis of the NPs into TEM's via the internalization of the membrane CD45RO tyrosine kinase. Consequently, the Cy3‐labeled siRNA encapsulated into the NPs was released into the cytosol. These finding set the foundation for a novel therapeutic approach in autoimmunity. (NIH R21AR060966)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.