Dissertations, Theses, and Capstone Projects

Date of Degree

9-2026

Document Type

Doctoral Dissertation

Degree Name

Doctor of Philosophy

Program

Biochemistry

Advisor

Uri Samuni

Committee Members

George John

Sanjai Pathak

Greg Phillips

Chen Wang

Subject Categories

Nanomedicine | Nanotechnology

Keywords

Nano-materials, Sol-gel, nanoparticles, cyclic nitroxides, TEMPO derivatives, MRI contrast agents, loading nanoparticles, silica nanoparticles

Abstract

Radiology tests are among the fastest-growing categories of diagnostic analysis, and the gold standard of radiology tests is MRI.  MRI can be more informative if a contrast agent is used, and the standard of care contrasting agents (CA) are gadolinium-based.  Gadolinium is a heavy metal, toxic, and contraindicated for renal-compromised patients and the critically ill.  We propose a nanogel (NG) vehicle for an alternative organic CA.  CNs like 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL) and its derivatives have a variety of medical and industrial uses.  These cyclic CNs are stable, synthetic radicals with distinctive EPR/ESR signals and are helpful for various experimental applications, from spin labeling to MRI/EPR tracing.  Nanogels (NGs) can serve as non-toxic, chemically inert vehicles to protect CNs.  However, some challenges are associated with using an NG carrier to deliver a cyclic CN (CN).  The extensive porosity of the NG matrix is in the nanometer range, and the size of the CN is on the Angstrom level. The size of the NG cargo, and the NG pores requires various physical and chemical strategies to permanently embed or tether the CN cargo the NG matrix.  This means that the CN incorporated into NG will elute out of the NG matrix unless some process is utilized for their permanent retention.  We report fabricating NG utilizing mainly the sol-gel synthesis for the NG vehicle itself, and two main approaches to NG loading: CN encapsulation and CN tethering.  CN encapsulation involves covalently bonding the CN to a larger molecule that can then become embedded within the NG pores.  CN tethering involves attaching the CN directly to the NG matrix.  Analytical methods we employ to ascertain NG size, shape, stability, solubility and toxicity, include dynamic light scattering, TEM imaging, Zeta potential analysis, solubility testing and yeast viability assays.  FTIR, and UV-vis spectroscopy are used to ascertain the extent of  CN loading quantitatively and qualitatively.  The approaches we developed, are innovative ways to load NG with small molecules.  Our data shows that were able to fabricate monodisperse, stable, non-toxic NG that contain the CN, and are soluble in aqueous medium to varying degrees.

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