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    cIBR effectively targets nanoparticles to LFA-1 on acute lymphoblastic T cells

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    Chittasupho_2010.pdf (1.232Mb)
    Issue Date
    2010-02-01
    Author
    Chittasupho, Chuda
    Manikwar, Prakash
    Krise, Jeffrey P.
    Siahaan, Teruna J.
    Berkland, Cory J.
    Publisher
    American Chemical Society
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    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.
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    Abstract
    Leukocyte 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.
    URI
    http://hdl.handle.net/1808/24022
    DOI
    https://doi.org/10.1021/mp900185u
    Collections
    • Pharmaceutical Chemistry Scholarly Works [339]
    Citation
    Chittasupho, 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/mp900185u

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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