The dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for developing efficient and safe therapies. The discovery of the anti-neoplastic activity in FTY720 (Gilenya ®), an FDA-approved drug for the treatment of multiple sclerosis, is a pinnacle for the world of chemotherapy. FTY720 has been shown to inhibit cancer progression through the down-regulation of essential nutrient transporter proteins, selectively inducing starvation and apoptosis in cancer cells. Although this novel approach to cancer therapy holds much promise, the instigation of bradycardia (decreased heart rate) and immune suppression brought on at the anti-neoplastic dose of FTY720 prohibits its application to cancer therapy. An acid-cleavable prodrug, FTY-k-PEG, was designed to limit the toxicity of FTY720 while possessing the capability to release the original drug utilizing low-cost, scalable synthetic methodology. Under physiological pH, FTY-k-PEG remains intact yet exhibits efficient hydrolysis in pH 5.0, with 81% of drug released after 28 hours. FTY-k-PEG demonstrated nearly identical efficacy in a Bcr-Abl + leukemia model without inducing bradycardia or lymphopenia.

Co-delivery of synergistic therapies within a single nano carrier can enhance efficacy, lower toxicity, normalize release profiles, and increase specificity. Synergism was explored between FTY720 and Dasatinib, a tyrosine kinase inhibitor currently used to treat Bcr-Abl+ leukemia, and an acid-cleavable prodrug formulation for Dasatinib was developed utilizing homo- and heterobifunctional ketal crosslinkers conjugated to a precursor with high efficiency and straightforward purification. A nanoparticle was designed to co-deliver FTY720, Dasatinib, and nucleic acid within an acid-degradable shell, previously shown to enhance endosomal escape. Lastly, methods were explored to maximize therapeutic efficacy and minimize waste by utilizing materials with restorative properties as the polymer backbone. Resveratrol is a well-studied antioxidant with chemical moieties suitable for polymerization and necessitates macromolecular-assisted delivery owing to its poor bioavailability. PRIMA-1 is a small-molecule drug designed to target mutant p53, a pro- apoptotic protein mutated in over 50% of all human cancers. Formulation for a co-polymer of RSV and PRIMA-1 was investigated to amplify therapeutic effects without increasing toxicity.

In summary, this dissertation explores synthetic methodologies to enhance current therapeutics by limiting toxicity and increasing efficacy.

In this dissertation a methodology for identifying and analyzing serial verb constructions (SVCs) is developed, and its application is exemplified through an analysis of SVCs in Koro, an Oceanic language of Papua New Guinea. SVCs involve two main verbs that form a single predicate and share at least one of their arguments. In addition, they have shared values for tense, aspect, and mood, and they denote a single event. The unique syntactic and semantic properties of SVCs present a number of theoretical challenges, and thus they have invited great interest from syntacticians and typologists alike. But characterizing the nature of SVCs and making generalizations about the typology of serializing languages has proven difficult. There is still debate about both the surface properties of SVCs and their underlying syntactic structure. The current work addresses some of these issues by approaching serialization from two angles: the typological and the language-specific.

On the typological front, it refines the definition of `SVC' and develops a principled set of cross-linguistically applicable diagnostics. From the existing set of surface properties, four core characteristics are distilled: main verbhood, monoclausality, single eventhood, and argument sharing. A construction must have all of these properties in order to qualify as an SVC. Once these underlying semantic and syntactic properties of SVCs are identified, a detailed and explicit set of criteria is developed that allows these underlying properties to be tested in any language.

The latter part of the dissertation offers a case study in the use of these diagnostic criteria by applying them to multi-verb constructions in Koro. Testing these constructions against the definition of SVCs developed in the dissertation reveals that although there are numerous multi-verb constructions in Koro that appear to fulfill the surface criteria for SVCs, only one of these can be considered a true SVC. This construction has a VP-shell structure, in which V1 is a path or locative verb that takes V2 as its complement. The shared argument is the subject of V2, providing a counter-example to Baker's (1989) claim that SVCs obligatorily share an internal argument. Constructions that instead involve adjunction of V2 to V1 are shown through detailed semantic investigation to be disqualified as SVCs, because they do not exhibit the expected entailments. This is surprising because they superficially resemble proto-typical SVCs. The syntactic and semantic analysis of these constructions leads to the hypothesis that true SVCs must have a relation of complementation between the verbs, while adjoined or coordinated constructions cannot be considered SVCs.