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I. 以同源性紅血球微囊當作氧化鐵之奈米載體應用於幹細胞磁振造影 II. 以適體結合之 DNA 二十面體奈米粒子作為抗癌藥物之載體用於癌症治療
Dissertation

I. 以同源性紅血球微囊當作氧化鐵之奈米載體應用於幹細胞磁振造影 II. 以適體結合之 DNA 二十面體奈米粒子作為抗癌藥物之載體用於癌症治療

張為棠
Doctor of Philosophy (PHD), 國立清華大學, 分子醫學研究所
2010

Abstract

紅血球微囊 磁振造影 奈米載體 人類骨髓間葉幹細胞 DNA 奈米粒子 阿黴素 超順磁氧化鐵粒子 二十面體 RBC-derived vesicles (RDVs) magnetic resonance imaging (MRI) Nanocarrier human bone marrow mesenchymal stem cells (MSCs) DNA nanoparticle doxorubicin ultrasmall superparamagnetic iron oxide (USPIO) icosahedra
I. To develop efficient and biosafe techniques for intracellular labeling with ultrasmall superparamagnetic iron oxide (USPIO) particles for cellular magnetic resonance imaging (MRI) is crucial for the development of successful stem-cell therapy. In this study we develop a novel system composed of RBC-derived vesicles (RDVs) for efficient delivering of USPIO particles into human bone marrow mesenchymal stem cells (MSCs) for cellular MRI in vitro and in vivo. The RDVs are highly biosafe to their autologous MSCs as manifested by cell viability, differentiation, and gene microarray assays. The data demonstrate the potential of RDVs as intracellular deliverers for biomedical applications. II. In the last decade, a series of reports have shown that DNA can be used to fabricate not only two-dimensional (2D) nanopatterns, but also three-dimensional (3D) polyhedra. A variety of applications of 3D DNA assemblies have been proposed; according to tensegrity principle that triangular faces will lead to rigid structures, DNA icosahedra would be expected to be rigid and resistant to deformations, hence could potentially serve as nanocages. Up to now, drug encapsulation and intracellular delivery using DNA nanoparticles remain a challenge. Here, we create a distinct five-point-star motif and aptamer-conjugated six-point-star motif using well-used primer sequences to intermolecularly construct DNA icosahedra as a nanocarrier for doxorubicin. Aptamer-conjugated doxorubicin-encapsulated DNA icosahedra (Doxo@Apt-DNA-icosa) show an efficient and specific internalization for killing epithelial cancer cells.

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