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Molecular Designs of Novel Responsive Assemblies for Therapeutic Delivery Applications

Stimuli responsive materials that predictably respond to a specific environment change through changes in their physicochemical properties have attracted attention due to potential applications in areas ranging from material science to biomedicine. Especially, stimuli responsive assemblies have been extensively investigated for drug delivery application as their flexibility, tunability and sensitivity to achieve desired properties such as the capability of acting as a host for encapsulation of guest molecules, the encapsulated drug can be programmed for release under specific stimulus relevant to the target site and thus increase the therapeutic efficiency of the drugs. These properties are critical and need to be customized really depending on the nature of delivered cargos and specific therapeutic applications. For instance, extended release of drugs is required for the treatment of chronic diseases, while a targeted and burst release is needed for diseases such as cancer and certain acute inflammatory diseases. More importantly, these properties are always desired to be adaptable in different environments as the biological barriers for drug delivery. The structure related properties need to be engineered to facilitate the delivery vehicle to overcome a variety of different biological barriers before it reaches the target site with subsequent releasing the payload in targets through a selective process. This dissertation will focus on the design of novel stimuli-responsive materials for therapeutic delivery applications. In Chapter 2-4, we will use different physical organic chemistry methods to systematically study different responsive materials through the structure-property relationship to tune the properties. Further, the correlation between these microscopic properties of polymer assembly and the custom-designed sensitive moieties were studied for delivery vehicles. Guided by understanding from this structure-property investigation, we aim on manipulating the polymer assembly using rationally designed stimuli-responsiveness as a handle to achieve desirable properties that are used for small molecule hydrophobic drug delivery in Chapter 5-6. Further, different molecular designs were used to prepare macromolecular drug delivery vehicles to achieve high therapeutic efficiency. In Chapter 7-10, different carriers were designed for protein delivery.
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