Full metadata
Title
Design of apoferritin-based nanoparticle MRI contrast agents through controlled metal deposition
Description
Sensitivity is a fundamental challenge for in vivo molecular magnetic resonance imaging (MRI). Here, I improve the sensitivity of metal nanoparticle contrast agents by strategically incorporating pure and doped metal oxides in the nanoparticle core, forming a soluble, monodisperse, contrast agent with adjustable T2 or T1 relaxivity (r2 or r1). I first developed a simplified technique to incorporate iron oxides in apoferritin to form "magnetoferritin" for nM-level detection with T2- and T2* weighting. I then explored whether the crystal could be chemically modified to form a particle with high r1. I first adsorbed Mn2+ ions to metal binding sites in the apoferritin pores. The strategic placement of metal ions near sites of water exchange and within the crystal oxide enhance r1, suggesting a mechanism for increasing relaxivity in porous nanoparticle agents. However, the Mn2+ addition was only possible when the particle was simultaneously filled with an iron oxide, resulting in a particle with a high r1 but also a high r2 and making them undetectable with conventional T1-weighting techniques. To solve this problem and decrease the particle r2 for more sensitive detection, I chemically doped the nanoparticles with tungsten to form a disordered W-Fe oxide composite in the apoferritin core. This configuration formed a particle with a r1 of 4,870mM-1s-1 and r2 of 9,076mM-1s-1. These relaxivities allowed the detection of concentrations ranging from 20nM - 400nM in vivo, both passively injected and targeted to the kidney glomerulus. I further developed an MRI acquisition technique to distinguish particles based on r2/r1, and show that three nanoparticles of similar size can be distinguished in vitro and in vivo with MRI. This work forms the basis for a new, highly flexible inorganic approach to design nanoparticle contrast agents for molecular MRI.
Date Created
2012
Contributors
- Clavijo Jordan, Maria Veronica (Author)
- Bennett, Kevin M (Thesis advisor)
- Kodibagkar, Vikram (Committee member)
- Sherry, A Dean (Committee member)
- Wang, Xiao (Committee member)
- Yarger, Jeffery (Committee member)
- Arizona State University (Publisher)
Topical Subject
Resource Type
Extent
xi, 132 p. : ill. (some col.)
Language
Copyright Statement
In Copyright
Primary Member of
Peer-reviewed
No
Open Access
No
Handle
https://hdl.handle.net/2286/R.I.15999
Statement of Responsibility
by Maria Veronica Clavijo Jordan
Description Source
Viewed on Oct. 7, 2013
Level of coding
full
Note
Partial requirement for: Ph.D., Arizona State University, 2012
Note type
thesis
Includes bibliographical references (p. 113-123)
Note type
bibliography
Field of study: Bioengineering
System Created
- 2013-01-17 06:41:46
System Modified
- 2021-08-30 01:43:36
- 2 years 8 months ago
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