Date of Award

1-1-2018

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Nanoscale Science and Engineering

Program

Nanoscale Engineering

Content Description

1 online resource (xiv, 125 pages) : color illustrations.

Dissertation/Thesis Chair

Nathaniel C Cady

Committee Members

Magnus Bergkvist, James Castracane, Andre Melendez, Benoit Boivin

Keywords

Bioconjugation, Blood-brain barrier, Drug Delivery, MRI, MS2 bacteriophage, Nanoparticle, Brain, Bacteriophages, Biological transport, Nanobiotechnology, Gadolinium, Drug targeting

Subject Categories

Biomedical Engineering and Bioengineering | Nanoscience and Nanotechnology | Virology

Abstract

Novel methods are needed to traverse the blood-brain barrier (BBB) and deliver drugs to specific targets in the brain. To this end, MS2 bacteriophage was explored as a multifunctional transport and targeting vector. The MS2 capsid exterior was modified with two different targeting moieties for delivery across the BBB and targeting specific regions of interest in the brain. Successful modification of MS2 capsids with a brain targeting peptide and NMDAR2D-targeting antibody was confirmed by immunoblotting and fluorescence detection. To measure transport efficiency of MS2 particles across an in vitro BBB model, a highly sensitive RT-qPCR protocol was developed and implemented. Finally, in order to demonstrate the potential of MS2 as a drug delivery vehicle, interior loading of capsids was investigated with the MRI contrast agent Gd- DOTA modified with psoralen. While the focus of this dissertation was to develop a nanoparticle platform toward a specific purpose, we have also developed a foundational toolkit for use with any system amenable to the functionalization chemistries and PCR protocols presented herein, ultimately offering longevity and further application of the techniques developed in these studies.

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