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    PEGylated PLGA nanoparticle delivery of eggmanone for T cell modulation: Applications in rheumatic autoimmunity

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    Author
    Haycook, C.P.
    Williams, C.H.
    Hong, C.C.
    Date
    2020
    Journal
    International Journal of Nanomedicine
    Publisher
    Dove Medical Press Ltd.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.2147/IJN.S234850
    Abstract
    Background: Helper T cell activity is dysregulated in a number of diseases including those associated with rheumatic autoimmunity. Treatment options are limited and usually consist of systemic immune suppression, resulting in undesirable consequences from compromised immunity. Hedgehog (Hh) signaling has been implicated in the activation of T cells and the formation of the immune synapse, but remains understudied in the context of autoimmunity. Modulation of Hh signaling has the potential to enable controlled immunosuppression but a potential therapy has not yet been developed to leverage this opportunity. Methods: In this work, we developed biodegradable nanoparticles to enable targeted delivery of eggmanone (Egm), a specific Hh inhibitor, to CD4+ T cell subsets. We utilized two FDA-approved polymers, poly(lactic-co-glycolic acid) and polyethylene glycol, to generate hydrolytically degradable nanoparticles. Furthermore, we employed maleimide-thiol mediated conjugation chemistry to decorate nanoparticles with anti-CD4 F(ab') antibody fragments to enable targeted delivery of Egm. Results: Our novel delivery system achieved a highly specific association with the majority of CD4+ T cells present among a complex cell population. Additionally, we have demonstrated antigen-specific inhibition of CD4+ T cell responses mediated by nanoparticle-formulated Egm. Conclusion: This work is the first characterization of Egm's immunomodulatory potential. Importantly, this study also suggests the potential benefit of a biodegradable delivery vehicle that is rationally designed for preferential interaction with a specific immune cell subtype for targeted modulation of Hh signaling. Copyright 2020 Haycook et al.
    Sponsors
    National Heart, Lung, and Blood Institute, NHLBI: T32HL144446 National Institute of Allergy and Infectious Diseases, NIAID: R03AI124190
    Keyword
    Advanced delivery systems
    Autoimmunity
    Controlled release
    Eggmanone
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85079886306&doi=10.2147%2fIJN.S234850&partnerID=40&md5=42d318f6dd038114cff0d18cd629ff5b; http://hdl.handle.net/10713/12162
    ae974a485f413a2113503eed53cd6c53
    10.2147/IJN.S234850
    Scopus Count
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