dc.creator | Haycook, Christopher Paul | |
dc.date.accessioned | 2020-08-24T11:53:51Z | |
dc.date.available | 2020-11-16 | |
dc.date.issued | 2018-11-16 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-11152018-173530 | |
dc.identifier.uri | http://hdl.handle.net/1803/15537 | |
dc.description.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. | |
dc.format.mimetype | application/pdf | |
dc.subject | immunoengineering | |
dc.subject | nanotechnology | |
dc.subject | lupus | |
dc.subject | immunotherapy | |
dc.subject | drug delivery | |
dc.subject | autoimmunity | |
dc.title | Development and Characterization of CD4+ T Cell Targeting Nanoparticles for Therapeutic Delivery of Immunomodulatory Drugs | |
dc.type | thesis | |
dc.contributor.committeeMember | Amy S. major | |
dc.type.material | text | |
thesis.degree.name | MS | |
thesis.degree.level | thesis | |
thesis.degree.discipline | Biomedical Engineering | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2020-11-16 | |
local.embargo.lift | 2020-11-16 | |
dc.contributor.committeeChair | Todd D. Giorgio | |