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  • 學位論文

螢光金奈米團簇探針之合成與應用

Synthesis and Application of Fluorescent Gold Nanocluster’s Probes

指導教授 : 張恒雄 林政鞍
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摘要


在奈米科技領域中,螢光奈米探針已廣泛使用於生物標記發展上,傳統以有機螢光染劑、量子點及螢光蛋白為主,在奈米生物醫學領域下以生物標定與造影成像極為重要。目前螢光金奈米團簇具有優越之光學性能、良好之生物相容性及不易光漂白特性,為研究上發展之重點。但螢光金奈米團簇之量子產率低且具有非特異鍵結於生物體內,是現今研究改善之重點。本研究利用長碳鏈硫醇基分子合成出高量子產率螢光金奈米團簇,並進行表面修飾與生物接枝特定功能之官能基,最後以生物標記證實其應用性。首先以簡單、快速方法合成出有機疏水相之螢光金奈米團簇,粒徑約為2 nm,並利用辛烯基丁二酸形成新型奈米相轉換之微乳化劑,以取代傳統具有生物毒性之表面活性劑。利用簡單、快速之微乳化相轉換方式,將任何有機疏水相之奈米粒子/團簇修飾為親水相結構。隨後以二硬脂酰基磷脂酰乙醇胺-聚乙二醇-葉酸結構,用於修飾辛烯基丁二酸之相轉換緩衝層,已改善非特異性鍵結情形,並賦予螢光金奈米團簇表面具有葉酸分子,用於標定特殊癌細胞,以探討螢光金奈米團簇是否靶向特定葉酸受體之癌細胞,達到癌細胞標記之能力。總之,本篇論文主要提出一種通用於任何奈米材料之新型微乳化劑,以改善經由相轉換技術後伴隨之非特異性鍵結與生物毒性,以提升奈米材料再生醫應用上之價值。

並列摘要


Fluorescent nanoprobes are rapidly gaining popularity, and will soon replace more traditional bio-markers – such as organic fluorescent dyes, fluorescent proteins and quantum dots – as the most commonly used contrast for imaging in the field of biomedical technology. Fluorescent gold nanoclusters (FGNCs) hold particular interest, as they are known for their superior optical properties, high biocompatibility, as well as great resistance to photobleaching. However, FGNCs have low quantum yield and bind nonspecifically when tested in vivo. In response to these flaws, we first show that using dodecanethiol (DDT) as the surface modifier can increase the quantum yield of these clusters. Secondly, to combat the lack of specificity of FGNCs, we ultimately modify the surface of the cluster to have a distearyl acyl phosphatidyl ethanolamine – polyethylene glycol – folic acid (DSPE-PEG-Folate) shell. Using a facile, efficient method, we synthesized biocompatible hydrophilic structured FGNCs from toxic, hydrophobic clusters with a diameter of two nanometers through the use of octenyl succinic anhydride (OSA) and microemulsion. This simple phase conversion process can not only be used to modify any organic hydrophobic nanoparticle or cluster into a hydrophilic structure, it also increases the efficiency of binding DSPE-PEG-Folate to the gold nanocluster. This counters the lack of specificity of FGNCs by allowing the particles to target certain folate receptors on cancers cells and illuminate their locations. Using a generic microemulsifier, OSA, we can decrease the biological toxicity and increase binding specificity of any nanomaterial through phase conversion technology and thus enhance the regenerative medical applications of nanotechnology.

參考文獻


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