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Author ORCID Identifier



Open Access Dissertation

Document Type


Degree Name

Doctor of Philosophy (PhD)

Degree Program


Year Degree Awarded


Month Degree Awarded


First Advisor

Thayumanavan, Sankaran

Subject Categories

Biochemistry | Inorganic Chemistry | Materials Chemistry | Medicinal-Pharmaceutical Chemistry | Organic Chemistry | Polymer Chemistry


The design and synthesis of responsive supramolecular assemblies are of great interest due to their applications in a variety of areas such as drug delivery and sensing. We have developed a facile method to prepare self-crosslinking disulfide-based nanogels derived from an amphiphilic random copolymer containing a hydrophilic oligo-(ethylene glycol)-based side-chain functionality and a hydrophobic pyridyl disulfide functional group. This thesis first provides a concept of studying the influence of Hofmeister ions on the size and guest encapsulation stability of a polymeric nanogel. The size and core density of nanogel can be fine-tuned through the addition of both chaotropes and kosmotropes during nanogel formation. We demonstrate that the change in core density can affect the guest encapsulation stability and stimuli-responsive character of the nanogel. Fluorescence resonance energy transfer (FRET) has been used as the tool to interrogate the guest-exchange process among varieties of host-guest assemblies, which has proved to be quite a robust method to gain insights regarding the guest encapsulation stability in these host assemblies. We studied the effect of host and guest environment upon the guest-exchange dynamics. By systematically comparing the behavior of pH-sensitive and pH-insensitive nanogels, we show that size, concentration, and hydrophobicity can all play a critical role in guest-exchange dynamics. More importantly, these studies reveal that the dominant mechanism of guest exchange can intimately depend on environmental factors. Nanocarriers that can be effectively transported across cellular membranes have potential in a variety of biomedical applications. We report a facile route to prepare nanogels, which generate surface charge with pH viii as stimulus due to the slightly acidic conditions observed in the extracellular environment of solid tumor. We show that the pH at which the charge is generated, i.e. the isoelectric point (pI) of the nanogel, can be easily adjusted. Intracellular delivery of these nanogels was greatly enhanced in an acidic pH environment due to the surface charge generation. This study demonstrates the versatile nature of the nanogels to introduce specific functionalities with relative ease to achieve desired functional behavior. Further, we have taken advantage of photo-induced heterodisulfide metathesis to develop a reagent-free synthetic method to generate self-crosslinking disulfide-based nanogels crosslinked polymer nanoparticles.

In addition, we report on a simple method to prepare monodisperse polymeric nanoparticles through sequential boronate esterification of boronic acids and bifunctional catechols under ambient conditions. Our results suggest that the initial polymer formation, serving as the nucleus for monodisperse nanoparticle assembly, involves a cooperative polymerization, wherein the dative bond between the nitrogen in the imine building blocks and the boron in the boronate ester plays a critical role. The dynamic nature of the dative interaction in this equilibrium self-assembly has been shown to endow these nanoparticles with thermal responsive characteristics. Further, hollow metal-organic nanoparticles (MOPs) were synthesized from these polymeric nanoparticles using a simple metal-comonomer exchange process in a single step. The Kirkendall effect has been identified as the underlying mechanism for the formation of these hollow MOPs, which also allows a unique opportunity to tune the shell thickness of the MOPs. The generality of the methodology is evident from that it is applied for a variety of metal ions with different coordination geometries.