Please use this identifier to cite or link to this item:
Type: Thesis
Title: Dendritic Cell Targeted Therapy Utilising Porous Silicon Nanoparticles for the Induction of Immunological Tolerance
Author: Stead, Sebastian Oliver
Issue Date: 2018
School/Discipline: Adelaide Medical School
Abstract: The work depicted in this thesis, explores the use of drug loaded porous silicon nanoparticles (pSiNP) targeted to dendritic cells both in vitro and in vivo. Paper one explores the in vitro application of rapamycin loaded, DC-SIGN pSiNP to induces a maturation resistant, tolerogenic state within human monocyte derived DC. Furthermore, it explores the poor stimulatory ability of these tolerogenic DC within an allogeneic immune system. The study concluded that nanoparticles functionalised with DC-SIGN antibody, were capable of tracking to human monocyte derived DC expeditiously compared to their isotype counterparts. DC-SIGN pSiNP were also able to release their payload and induce a tolerogenic state in DC in vitro. Paper two develops the work from paper one exploring the in vivo tracking capability of the nanoparticle within both murine and non-human primate animal models. Within mice, the functionalisation of the pSiNP with antibodies permitting targeting to DC (CD11c receptor) significantly enhanced their tracking abilities to splenic DC populations, compared to isotype pSiNP. Within both murine and nonhuman primate animal models, a serendipitous discovery was the enhanced kidney tracking abilities of the DC targeting pSiNP. This opens the door for the development of potentially new drug delivery methods more localised to the kidneys. Following in vivo tracking experiments, paper two explored the ability of drug and peptide loaded nanoparticle to enhance regulatory T-cell populations in vivo by targeting DC. It was concluded that the CD11c pSiNP were capable of significantly increasing the number of splenic regulatory T-cells when compared to the control animals, which did not receive pSiNP. These two papers identify a novel strategy for promoting drug delivery to a scarce cell population and the ability to promote regulatory T-cell generation in vivo without ex vivo modification of DC, which is more commonly seen today. The results show promise for future development of an enhanced drug delivery method to modify the immune system.
Advisor: Coates, Toby
Voelcker, Nico
Carroll, Robert
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2018
Keywords: Nanoparticles
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at:
Appears in Collections:Research Theses

Files in This Item:
File Description SizeFormat 
Stead2018_PhD.pdf5.55 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.