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    Development and Characterization of CD4+ T Cell Targeting Nanoparticles for Therapeutic Delivery of Immunomodulatory Drugs

    Haycook, Christopher Paul
    : https://etd.library.vanderbilt.edu/etd-11152018-173530
    http://hdl.handle.net/1803/15537
    : 2018-11-16

    Abstract

    T cell activity is dysregulated in a number of autoimmune diseases for which systemic lupus erythematosus is a prime example. Treatment options are limited and usually consist of overt immune suppression and compromised immunity. A potential mechanism for autoimmune lymphocyte survival is dysfunctional hedgehog (Hh) signaling. Hh signaling is implicated in the activation of CD4+ T cells and the maintenance of germinal center B cells, while dysfunctional Hh signaling is associated with human autoimmunity. In this work we developed CD4 targeted, biodegradable nanoparticles from FDA-approved polymers to enable therapeutic delivery of eggmanone, a Hh inhibitor discovered at Vanderbilt University. We were able to achieve high levels of CD4+ T cell targeting specificity and minimal non-specific particle binding. Furthermore, we have demonstrated antigen specific inhibition of CD4+ T cell activation mediated by nanoparticle formulated eggmanone. Collectively, this work represents the research and development of a rationally designed nanoparticle delivery vehicle intended for therapeutic administration of eggmanone, and other hydrophobic agents with immunomodulatory potential, to CD4+ T cells.
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