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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

Sankaran Thayumanavan

Subject Categories

Organic Chemistry


Stimuli-responsive systems have attracted wide interest due to their applications in a variety of areas such as drug delivery and sensing. Stimuli-responsive systems that are triggered by secondary biological changes have been studied extensively. Primary biological changes, such as protein imbalances and enzymatic activity, are intrinsic to certain types of diseases, and thus have drawn increasing attention in triggering stimuli-responsive systems in areas such as drug delivery. This thesis first provides a concept of increasing stimuli-responsive selectivity by designing a system that only responds in the concurrent presence of two complementary primary biological stimuli, protein and enzyme. A dendritic assembly platform was used to test this concept. Each dendron was equipped with a protein specific binding ligand and an enzymatic responsive moiety. The results showed release of the report units that were covalently attached to dendrons when two stimuli concurrently presented, while no obvious release was observed with one trigger alone. By locking the aggregates in their aggregated state, this response is turned off, and unlocking the assembly resumes the dual triggered disassembly process. With the need to test the concept of dual triggered release without covalently attached report units, the thesis also investigated the above-mentioned concept with non-covalently attached dye molecules as report units, as in a real-life application, synthesis of a prodrug is not always feasible. Again, the studies showed faster initial rate of release and more overall release with two stimuli in comparison to one stimulus alone. Mix micelles, a system that mixed two dendrons with different protein specific binding ligand, were prepared to introduce a multi-stimuli responsive feature. The results showed mix micelles can respond to two protein stimuli as well as to enzymatic activity. Stable and size-tunable aggregates are also drawing the attention of the scientific community for utilization in a variety of applications in biomaterials and sensing materials. This thesis also demonstrates the design of aggregates whose size is tunable by taking advantage of the lower critical solution temperature (LCST) behavior of polyethylene glycol (PEG). The aggregates were then crosslinked through thiol-yne Click chemistry to stabilize the aggregate size, and upon incorporating the appropriate stimulus, the crosslinked aggregates were disassembled.