Chemistry Commons^™

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov

Doctoral Dissertations

Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …

Developing Injectable And Implantable Polymer Zwitterion Platforms For Glioblastoma Treatment, Sarah Ward

Doctoral Dissertations

This dissertation describes the synthesis, characterization, and application of novel polymer zwitterion-drug conjugates intended for treating glioblastoma, with a particular focus on phosphorylcholine (PC) and temozolomide (TMZ). Using versatile TMZ-containing monomers, injectable polymer prodrugs and implantable polymeric hydrogels were prepared over a broad range of drug incorporations with tunable properties, making them ideally suited for further in vivo and clinical evaluations. The work presented here greatly expands the knowledge base of TMZ formulations and gives rise to several routes which circumvent the challenges associated with its use. Chapter 2 describes the incorporation of a novel TMZ-methacrylate monomer into random and …

Hybrid Micellar Network Hydrogels Of Thermosensitive Hydrophilic Triblock Copolymers And Thermosensitive Hairy Nanoparticles, Bin Hu

Doctoral Dissertations

Hybrid micellar network hydrogels, composed of thermosensitive hydrophilic triblock copolymers and thermosensitive polymer brush-grafted nanoparticles (hairy NPs), exhibit intriguing rheological properties. This dissertation work studies thermosensitive hybrid hydrogels with NPs positioned either inside or outside the core of block copolymer micelles.

Chapter 1 is an introduction. Chapter 2 examines the effect of NP’s location on properties of hybrid hydrogels of a thermosensitive ABA triblock copolymer and hairy NPs. Two batches of thermoresponsive polymer brush-grafted silica NPs and an ABA triblock copolymer with thermosensitive outer blocks were prepared. When the lower critical solution temperature (LCST) of hairy NPs was similar to …