Growth Effects of Major Land Use Projects (Wastewater Facilities): Model Specification and Causal Analysis, Vol. 1

The work described in this thesis is focused on the design, characterization, and application of synthetic materials that can be used to manipulate and control the delivery of biomacromolecules such as DNA and proteins to cells. The work described herein was conducted in two primary contexts: (1) the fabrication and characterization of multilayered films comprised of DNA and degradable polyamines, with applications to the surface-mediated delivery of DNA and proteins, and (2) the formation of self-assembled aggregates of DNA and redox-active lipids that could allow active control over the delivery of DNA. The first approach described in this thesis is based on the layer-by-layer assembly and characterization of thin films fabricated from hydrolytically-degradable polyamines and biomacromolecules. When contacted with cells in culture, these assemblies permit the surface-mediated delivery of DNA and proteins and may prove useful in the development of methods seeking the localized delivery of therapeutics. Additional work involving DNA-containing multilayered films deposited on the surfaces of biomedical devices such as intravascular stents has demonstrated that these assemblies are able to withstand mechanical stresses similar to those associated with stent deployment in vivo, and further, that film-coated stents are able to mediate high levels of cell transfection in vitro. The second approach described in this thesis demonstrates that lipoplexes formed from DNA and a ferrocene-containing, redox-active cationic lipid can be used to control the delivery of DNA to cells in ways that depend critically upon the redox-state of the lipid. Additional studies demonstrate that these assemblies can be chemically transformed from an inactive state (e.g., a state this is unable to mediate cell transfection) to an active state (e.g., a state that mediates high levels of cell transfection) using a chemical reducing agent. This approach could thus serve as a platform for exerting spatial, temporal, and/or active control over the delivery of DNA.

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