Enzymatic protein labeling and polymeric materials for cancer-therapy and anti-fouling applications

Abstract

This dissertation focused on two relevant topics, cancer and antifouling. Cancer was chosen as the first target since despite the long-standing substantive efforts, it remains one of the most challenging malignant diseases. For instance, still to this date, brain cancer has a five-year survival rate of 12.8%. Two different approaches were studied to tackle cancer. In one aspect, enzymatic labeling was exploited in synthesizing protein-based therapeutics capable of cancer-targeted imaging and drug delivery. Having multiple therapeutic payloads loaded to a site-specifically conjugated hydrophilic polymer allowed highly retained cancer-binding affinity of the target protein DARPin. Therefore, the protein product exhibited high therapeutic efficacy. In another aspect, novel stimuli-responsive hydrogels were developed to understand the underlying mechanism of brain cancer metastasis. The mechanical properties of the gel could be spatiotemporally controlled with high-resolution, enabling the study of durotaxis, which is a biased directional movement of brain cancer cells. Combined with microbiological and computational studies, new insights into cellular behavior that were acquired as a result of the new hydrogel platform revealed the molecular components and their dynamics that dictate durotaxis. On a different topic, antifouling applications were explored, which is another relevant issue, especially in the marine and health care industry. Quorum quenching enzymes were site-specifically modified via protein farnesyltransferase for visualization or immobilization purposes. The modification that allows high retention of the protein activity allowed various biotechnological applications of the quorum quenching enzyme. Overall, interdisciplinary research that involves chemical biology, polymer chemistry, and organic chemistry, was utilized to study important present-day issues.