Thesis (M. Phil.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Thesis (Ph. D.)--Lehigh University, 1999. / Includes vita. Bibliography: leaves 89-105.

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1991. / Vita. Abstract. Includes bibliographical references (leavea 118-121). Also available via the Internet.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 162-182) Also available online.

Thesis (Ph. D.)--University of Texas at Austin, 2004. / Vita. Includes bibliographical references.

Thesis (M.Phil.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 134-145) Also available in print.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Typescript. Vita. Includes bibliographical references.

Thesis (M.A.)--York University, 2005. Graduate Programme in Kinesiology and Health Science. / Typescript. Includes bibliographical references (leaves 89-92). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url%5Fver=Z39.88-2004&res%5Fdat=xri:pqdiss &rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR11878

Thesis (Ph. D.)--University of Hong Kong, 2007. / Also available online.

Paclitaxel (PTX) is among the most commonly used first-line drugs for cancer chemotherapy. However, its poor water solubility and indiscriminate distribution in normal tissues remain clinical challenges. Here we designed and synthesized a highly water-soluble nucleolin aptamer-paclitaxel conjugate (NucA-PTX) that selectively delivers PTX to the tumor site. By connecting a tumor-targeting nucleolin aptamer (NucA) to the active hydroxyl group at 2' position of PTX via a cathepsin B sensitive dipeptide bond, NucA-PTX could remain stable and inactive in the circulation. The tumor-recognition component NucA facilitates the uptake of the conjugated PTX specifically in tumor cells. Once inside cells, the dipeptide bond linker of NucA-PTX will be cleaved by cathepsin B and then the conjugated PTX will be released for action. The stability of NucA-PTX in human serum and the cathepsin-B dependent release of the conjugated PTX in tumor cells were verified by monitoring the fluorescence resonance energy transfer (FRET) of a dual fluorescence-labeled conjugate FAM-NucA-PTX-Rd. In addition, the PTX conjugation did not considerably affect the binding affinity between NucA and its target protein nucleolin, which was supported by both molecular dynamic simulation and isothermal titration calorimetry (ITC). The NucA modification was shown to facilitate the uptake of the conjugated PTX in ovarian cancer cells mainly by macropinocytosis in a nucleolin expression-dependent manner. Moreover, the NucA modification increased the in vitro cytotoxicity and mitosis inhibition of the conjugated PTX in ovarian cancer cell lines. The in vivo data collected from a human xenograft model of ovarian cancer demonstrated that the NucA modification facilitated the selective accumulation of the conjugated PTX in ovarian tumor tissue, and subsequently resulting in notably improved antitumor activity and reduced toxicity.