http://hdl.handle.net/1721.1/3654 2013-05-20T00:16:57Z http://hdl.handle.net/1721.1/30395 Template Synthesis of Tubular Sn-Based Nanostructures for Lithium Ion Storage Wang, Yong; Zeng, Hua Chun; Lee, Jim Yang We report herewith the preparation of SnO₂ nanotubes with very good shape and size control, and with and without a carbon nanotube overlayer, The SnO₂-core/carbon-shell nanotubes are excellent reversible Li ion storage compounds combining the best features of carbon (cyclability) and SnO₂ (capacity) to deliver a high specific capacity (~540-600 mAh/g) simultaneous with good cyclability (0.0375% capacity loss per cycle). 2006-01-01T05:00:00Z http://hdl.handle.net/1721.1/30394 Targeted Stimuli-Responsive Dextran Conjugates for Doxorubicin Delivery to Hepatocytes Zaman, Noreen T.; Tan, Fred E.; Joshi, Shilpa M.; Ying, Jackie Y. A targeted, stimuli-responsive, polymeric drug delivery vehicle has been developed to help alleviate the severe side-effects caused by narrow therapeutic window drugs. Doxorubicin, a commonly used chemotherapeutic agent has been conjugated to dextran by two different techniques. In the first method, doxorubicin and hepatocyte-targeting galactosamine were attached to dextran through amine bonds. Conjugation efficiency based on the amount loaded of each reactant varied from 1% to 50% for doxorubicin and from 2% to 20% for galactosamine, depending on various synthesis parameters. For the second conjugate, doxorubicin was attached to dextran through an acid-labile hydrazide bond. Fluorescence quenching indicated that all our conjugates can bind to DNA. The degree of binding was improved with increasing polymer molecular weight and substitution of doxorubicin, and also with hydrazide-bonded conjugate. In cell culture experiments, we have found that the uptake of conjugates was much lower than that of free doxorubicin. Lower uptake of conjugates decreased the toxicity of doxorubicin. Also, the uptake of non-galactosylated conjugate was lower than that of the galactosylated conjugate. Microscopy studies indicated that doxorubicin was localized almost exclusively at the nucleus, whereas the amine-bonded conjugates were present throughout the cell. Targeted amine-linked conjugates and hydrazide-bonded conjugates achieved greatly improved cytotoxicity. Following uptake, the doxorubicin was dissociated from the hydrazide conjugate in an endosomal compartment and diffused to the nucleus. The LC₅₀ values of non-targeted amine-linked, targeted amine-linked, and hydrazide-linked doxorubicin were 19.81 μg/mL, 7.33 μg/mL and 4.39 μg/mL, respectively. The amine-linked conjugates were also tested on a multidrug-resistant cell line; the LC₅₀ values of doxorubicin and the non-targeted amine-linked conjugate were 8.60 μg/mL and 36.02 μg/mL, respectively. 2006-01-01T05:00:00Z http://hdl.handle.net/1721.1/30393 Synthesis and Self-assembly of [60]Fullerene Containing Sulfobetaine Polymer in Aqueous Solution Ravi, P.; Dai, S.; Tam, K. C. A series of well-defined stimuli responsive water soluble [60]fullerene (C₆₀) containing polymers such as polyelectrolytes (polyacids and polybases), polyampholyte and polyzwitterionic polymers were synthesized using atom transfer radical polymerization. The aqueous solution properties of these polymers with respective external stimuli such as pH, temperature and salt were studied using potentiometric and conductivity titration, light transmittance, laser light scattering and transmission electron microscopic techniques. The influence of polymer concentration, temperature, pH and electrolyte on the hydrodynamic radius (Rh), radius of gyration (Rg) and aggregation number (Nagg) of the particles were investigated in detail to elucidate the morphology of the particles. The morphology of the aggregates was further confirmed by the TEM micrographs. The cytotoxicity of the pH responsive C₆₀ containing well-defined polymers (PAA-b-C₆₀, C₆₀-b-PAA-b-C₆₀ and PEO-b-PAA-b-C₆₀) was studied to confirm the suitability of these particles as potential drug delivery vehicles. The binding interaction between the anti-cancer drug (doxorubicin) and C₆₀ containing pH responsive polymers was studied using isothermal titration calorimetry, and the implication of the results will be discussed. 2006-01-01T05:00:00Z http://hdl.handle.net/1721.1/30392 Study of GDNF-Family Receptor Alpha 2 And Inhibitory Activity of GDNF-Family Receptor Alpha 2b (GFRα2b) Isoform Yoong, Li Foong; Too, Heng-Phon The glial cell-line derived neurotrophic factor (GDNF) and neurturin (NTN) belong to a structurally related family of neurotrophic factors. NTN exerts its effect through a multi-component receptor system consisting of the GDNF family receptor alpha 2 (GFRα2), proto-oncogene RET and/or NCAM. GFRα2 is spliced into at least three isoforms, GFRα2a, GFRα2b and GFRα2c. The present study investigated the expression and functional differences of GFRα2 isoforms. These receptor isoforms are differentially expressed in specific human brain regions. Using Neuro2A model, GDNF and NTN promote neurite outgrowth via GFRα2a and GFRα2c, but not GFRα2b. These GFRα2 isoforms regulate different early response genes when stimulated with GDNF and NTN. Interestingly, using co-expression models, GFRα2b inhibits ligand induced neurites outgrowth of GFRα2a and GFRα2c, and also the related receptor, GFRα1a. More intriguingly, ligands activated GFRα2b was also able to attenuate neurite extension induced by an unrelated stimulation using retinoic acid. MAPK activation induced by GDNF was not attenuated by GFRα2b in a co-expression model, while the early response genes expression profile (up-regulation of FosB) was similar to that induced by GFRα2b alone. This study suggest that GFRα2b is not merely a dominant negative isoform, but signals through a yet to be determined mechanism to antagonize and inhibit neuritogenesis. Together, these data suggest a new paradigm for the regulation of growth factor signaling and neurite outgrowth via an inhibitory splice variant of the receptor. 2006-01-01T05:00:00Z