Abstract
Cancer is a widely known malignant neoplasm with high mortality. This disease has been extensively investigated in clinical and mechanistic studies. However, the occurrence and development of cancer remain imperfectly understood. The inner mechanism of cancer has also been continuously explored to cure this malignant disease. For this purpose, this thesis applied engineering tools, such as laser scissors, optical tweezers, and magnetic-aided delivery system, to treat cancer cells, to evaluate the alteration in biological functions, to characterize the underlying disease mechanism, and to explore a new therapeutic strategy for cancer treatment. This research was conducted on the basis of the following three aspects.First, a cancer cell–stem cell pair was precisely fused by using a laser-induced single-cell manipulation system consisting of optical tweezers, laser scissors, and a cell isolation system to explore the relationship between cancer cells and stem cells. After the cells were cultured, the biological functions of the fused cells were examined in vitro and in vivo. Experimental results showed that the fusion with the stem cells induced the cancer cells to act like a cancer stem cell. Thus, cancer cells demonstrated an increased resistance to treatment and enhanced tumorigenesis.
Second, cell-to-cell interaction was investigated by using a receptor–ligand-mediated cell adhesion tool, which was developed using an optical tweezers-based cell manipulation system. In a case study, the mechanism of the interaction between leukemia cells and stromal cells was probed by inhibiting receptor–ligand binding via a specific drug, and adhesion contact was controlled by assembling leukemia cells at different positions of stromal cell layers by using optical tweezers. Results indicated that the distribution and amount of adhesion molecules could largely affect cell adhesion.
Third, a magnetic-based delivery system composed of a magnetic glass rod and a magnet was developed for gene modification and drug delivery in cancer cell. The cell manipulated by such a system experienced compression and stretching forces exerted by the magnetic glass rod. Transient holes were also created on the cell membrane. Experimental results verified that this simple method could efficiently deliver plasmid DNA, fluorescein isothiocyanate-dextran, or differently sized fluorescent spheres into cells at a low cost.
In summary, a single-cell manipulation technology can be effectively used to characterize cell-based mechanisms and perform other procedures, including probing the primary mechanism of turmorigenesis, identifying the functions of cell organelles and special proteins, and promoting gene exchange. With the development of magnetic-based delivery technology, the delivery of biomaterials, such as DNA and protein drugs, has been simplified and costs have been reduced. This study has successfully demonstrated the effectiveness of applying engineering methods to investigate cancer mechanisms at a single-cell level and to explore a new therapeutic strategy by modifying gene expression or drug delivery.
| Date of Award | 5 Aug 2016 |
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| Original language | English |
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| Supervisor | Dong SUN (Supervisor) |