| Summary: | 碩士 === 國立中央大學 === 化學工程與材料工程學系 === 107 === Genetic diseases arise from abnormalities in genome. A promising approach in treating these diseases is employ a non-viral vehicle to compact and encapsulate therapeutic DNAs and deliver them into cells to repair the genetic disorders; gemini surfactants are among the most anticipated candidates for the gene delivery vehicle. Generally, the complexes formed by DNAs and vehicles enter cells by endocytosis. The endosomes formed during endocytosis encapsulate the complexes and become increasingly acidic to break down the internalized substances. As a result, a successful vehicle needs to maintain its structural integrity in an acidic environment to protect the DNAs from degradation and simultaneously escape from the endosome to release the DNAs for the transfection to occur. Earlier studies found that pH-sensitive gemini surfactants, when deployed as gene delivery vehicles, achieved higher transfection efficacies than their pH-insensitive counterparts. It is speculated that the higher transfection efficacy results from the former’s better capability to escape from endosomes. However, experimental evidence, whatever direct or indirect, remains lacking, let alone the understanding of the underlying molecular mechanisms. To address the issues, this study employs UV spectroscopy, atomic force microscope, and small-angle x-ray scattering to examine how the two types of gemini surfactants modify the conformations of DNAs; and employs fluorescence spectroscopy and small-angle x-ray and neutron scattering techniques to examine the extents of the DNA release from the vehicles and structural perturbations on the endosome-mimicking liposomes. Through comparing the differences in these aspects between the two types of geminni surfactants, we uncover the molecular mechanism accounting for the high transfection efficacy of the pH-sensitive gemini surfactants.
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