Date of Award

Spring 2018

Degree Type





Ellane Park

Second Advisor

James Patron

Third Advisor

Pedro Bernal


The development of multidrug-conjugated polymeric nanoparticles for drug delivery applications promises more effective forms of cancer therapy based on the target-specific, triggered release of therapeutic agents at the tumor site. Discrimination between healthy tissue and tumor cells can be achieved by exploiting the characteristics of the mildly acidic tumor microenvironment. While previous studies showed the potential of acid-responsive polymeric nanoparticles, low drug-loading and failure to release drugs in response to tumor-specific pH conditions remain a challenge in drug delivery and synthetic chemistry. This work presents the synthesis of acid-degradable star-like polymeric nanogels that allow high drug-loading and acid-triggered core degradation in tumor tissue based on the brush-first ring-opening metathesis polymerization (ROMP) method. These brush-arm star polymer (BASP) nanogels are composed of two monomers: (1) poly(ethylene glycol) (PEG) norbornene-terminated macromonomer providing biocompatible and water-soluble features and (2) the acid-cleavable acetal-based cross-linker enabling acid-triggered core degradation. After brush formation of PEG macromonomer resulting in the hydrophilic shell, a mixture of PEG macromonomer and cross-linker initiates the formation of the gel-like core via cross-linking. BASP nanogels were successfully synthesized using various ratios of cross-linker to PEG macromonomer. Characterization via gel permeation chromatography (GPC) confirmed the formation of mostly monomodal BASP nanogels with decreasing MW as the amount of PEG macromonomer is increased. Additional GPC analysis of acid degraded BASP nanogels suggests that the macromonomer increases the steric hindrance during cross-coupling and core formation resulting in smaller BASP nanogels. Furthermore, fluorescence studies show the successful loading of a fluorescein dye into BASP nanogel.

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