Chittasupho, ChudaManikwar, PrakashKrise, Jeffrey P.Siahaan, Teruna J.Berkland, Cory J.2017-05-082017-05-082010-02-01Chittasupho, C., Manikwar, P., Krise, J. P., Siahaan, T. J., & Berkland, C. (2010). cIBR effectively targets nanoparticles to LFA-1 on acute lymphoblastic T cells. Molecular Pharmaceutics, 7(1), 146. http://doi.org/10.1021/mp900185uhttps://hdl.handle.net/1808/24022Leukocyte function associated antigen-1 (LFA-1) is a primary cell adhesion molecule of leukocytes required for mediating cellular transmigration into sites of inflammation via the vascular endothelium. A cyclic peptide, cIBR, possesses high affinity for LFA-1 and conjugation to the surface of poly(dl-lactic-co-glycolic acid) nanoparticles can specifically target and deliver the encapsulated agents to T cells expressing LFA-1. The kinetics of targeted nanoparticle uptake by acute lymphoblastic leukemia T cells was investigated by flow cytometry and microscopy and compared to untargeted nanoparticles. The specificity of targeted nanoparticles binding to the LFA-1 integrin was demonstrated by competitive inhibition using free cIBR peptide or using the I domain of LFA-1 to inhibit the binding of targeted nanoparticles. The uptake of targeted nanoparticles was concentration and energy dependent. The cIBR-conjugated nanoparticles did not appear to localize with lysosomes whereas untargeted nanoparticles were detected in lysosomes in 6 hrs and steadily accumulated in lysosomes for 24 hrs. Finally, T-cell adhesion to epithelial cells was inhibited by cIBR-nanoparticles. Thus, nanoparticles displaying the cIBR ligand may offer a useful targeted drug delivery system as an alternative treatment of inflammatory diseases involving transmigration of leukocytes.This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/mp900185u.LFA-1LeukocytesPeptideNanoparticlesTargetingArticle10.1021/mp900185uPMC2815130openAccess