The Therapeutic Nanomaterials Applied in Bacteria, Cancer Cells and Stem Cells
| Autor: | Wen-Shuo Kuo, 郭文碩 |
|---|---|
| Rok vydání: | 2009 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 97 This thesis is principally emphasized that therapeutic nanomaterials applied in bacteria, cancer cells and stem cell. We discuss it for four parts and they are bacteria coated Au nanoshells as photothermal agent in cancer cells, antimicrobial gold nanorods with dual-modality photodynamic inactivation and hyperthermia, paclitaxel loaded poly(D,L-lactide-co-glycolide) nanoparticles for reversion of drug resistance and cancer cellular imaging, poly(lactide-co-glycolide) as a potential carrier applied in human mesenchymal stem cells, respectively. Part 1, when the E. coli bacteria were incubated with HAuCl4 precursors without the addition of a reducing agent, gold nanoshells were generated and covered the bacteria surface. Interestingly, the bacteria coating with gold nanomaterials remained alive and showed no toxicity to the tested mammalian cells. Gold nanoshell formation rendered E. coli inactive. The bacteria@Au composites exhibited near infrared (NIR) absorption and can be applied to photothermal therapy. The bacteria@Au composites can be conveniently conjugated with anti-EGFR antibodies for targeted NIR photothermal destruction of cancer cells. These results might provide an intriguing method to use bacteria and bacteria@Au composites in biomedical applications. Part 2, polyacrylic acid (PAA) polymer and a hydrophilic photosensitizer, TBO, were conjugated on the surface of Au nanorods. The resulting Au-PAA-TBO nanorods served as photodynamic and hyperthermia agents. Combined PACT and hyperthermia more efficiently killed bacteria compared with PACT or hyperthermia treatment alone, and it improved antimicrobial efficiency. Part 3, we have demonstrated to synthesize paclitaxel-loaded PLGA-QD655 nanoparticles then showed that loading PLGA nanoparticles with paclitaxel resulted in greater cellular drug uptake, sustained intracellular drug retention, and decreased the proliferation of paclitaxel-treated cancer cells. The data with paclitaxel-loaded nanoparticles in a drug resistant cell line suggest not only that drug resistance can be overcome by sustaining intracellular drug retention, but also that the paclitaxel-resistant cell line we used is associated with MDR mechanisms. We showed that conjugating quantum dots with PLGA nanoparticles turns the PLGA nanoparticles into molecular imaging probes. Paclitaxel-loaded PLGA-QD655 nanoparticles seem to be a new therapeutic tool for curing cancers, and PLGA nanoparticles coated with quantum dots appear to be useful for additional biomedical applications. Part 4, we have successfully labeled hMSCs with PLGA-QD NPs. The MTT cytotoxic investigation and ROS analysis both showed that these NPs exhibited a good cytocompatibility. Qualitative and semi-quantitative flow cytometry and ICP results indicated that the maximum internalization of NPs in cells was achieved within 3 hours of incubation and can be retained for long periods of time. Moreover, NPs labeling did not hinder the proliferation and differentiation capability of hMSCs. From the results of the substrate-encapsulated delivery system, we demonstrate that PLGA NPs can indeed be used as nano-carriers to release encapsulated materials in stem cells. In the future, it is promising that PLGA NPs will not only be used as nano-capsules to load drugs that induce stem cell differentiate into specific cells or genes that express desired proteins but they will also be used for controlled release of biomaterials. It is concluded that these experiments may lead to further applications of PLGA in stem cell therapy. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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