新型螢光金奈米團簇與馬來酸酐兩性高分子披覆之奈米探針設計與生醫應用

Design of Novel Nanoprobes Using Fluorescent Gold Nanoclusters and Poly(Maleic Anhydride) Derivatives of Amphiphilic Polymer Coating toward Biomedical Application

林政鞍(Cheng-An Lin)

指導教授 ： 張恒雄

中原大學/工學院/生物醫學工程學系/博士(2008年)

https://doi.org/10.6840/cycu200800393

摘要

奈米材料表面技術為奈米生物工程發展之重要核心。本論文先以量子點生醫技術的發展，介紹此新領域如何在近十年內，由科學技術創新發展成為極具產業利用價值的產品，包含量子點合成、水相改質及官能化及如何賦予生物相容性與生物功能性完整之回顧(第二章)，讓讀者藉由量子點技術演進為例了解奈米生物工程。目前量子點技術發展皆歸功於Alivisatos 和Nie兩位學者實驗室，於1998年所發展出之水相改質技術，此項表面化學技術的揭露，成功媒合物理、化學與生物醫學研究整合。故本論文提出適用於各種疏水奈米材料披覆之兩性高分子設計，作為奈米材料生醫應用之橋樑，文中主要描述以馬來酸酐高分子自動嫁接疏水碳鏈及生物分子(聚乙二醇、半乳糖、生物素等)之製備流程，成功應用於功能性奈米材料(量子點、奈米金、氧化鐵奈米粒子)之水相改質及官能化(第三章)。另外，由於量子點含有有毒重金屬(鎘、鉛)成分，在醫學應用上正受到限制，我們於第二章也回顧了目前綠色(環保)量子點的發展，通常指所使用的奈米材料具有環境安全性、生物相容性、無毒性重金屬及可調控的螢光，更重要的，它必須克服未來臨床應用及環境健康所帶來長期毒性問題。因此本論文亦發展新型螢光金奈米團簇以填補半導體量子點之不足，第四章將充分介紹此新型螢光金奈米團簇之合成、水相改質及生物接枝，並包含成功標定細胞之範例。總之，本博士論文主要提出奈米生醫探針設計之通用技術，提昇奈米材料生醫應用之價值，提供臨床生醫研究重要工具。

關鍵字

奈米團簇 ； 奈米粒子 ； 量子點 ； 聚乙二醇 ； 兩性高分子 ； 生醫探針

並列摘要

Surface modification on nanomaterials is the core technology to develop nanobioengineering. Firstly, the thesis reviews the current progress of nanobiotechnology using quantum dots as examples, including synthesis, phase transfer, surface modification, biocompatibility and in vivo application. The reader can get full images how quantum dots become commercial available products from laboratory. Alivisatos and Nie et al, two most famous pioneering groups, have introduced a powerful interface technology adapting physicist, chemist, and biomedical researcher using quantum dots from 1998. Based on these pioneering works, the thesis propose a general amphiphilic polymer design for coating different kinds of nanomaterials, bridging the biological application of nanomaterials. The poly(maleic anhydride) are found as excellent backbone polymer of which can link hydrophobic alkyl chain as well as (bio-)molecules (polyethylene glycol, galactose, biotin, fluorescein and etc.) through a spontaneous amidation. Hydrophobic nanomaterials not only become water-soluble but get surface functionality right after polymer coating. Secondly, the quantum dots containing toxic ions have restricted their broad application in biomedical research, especially in clinics. The development of “greener” quantum dots, compatible to environments and human body, might solve the current crisis of traditional quantum dots. The thesis also introduces novel fluorescent gold nanoclusters from synthesis, ligand exchange, bioconjugation and cell labeling, giving a overall strategy to use fluorescent gold nanoclusters. In a word, general nanoprobes designs have been fully unveiled in this thesis and are expected to bring many biomedical applications.

並列關鍵字

nanoparticle ； nanoprobe ； quantum dot ； amphiphilic polymer ； nanocluster ； polyethylene glycol

參考文獻

Chapter 1:

1. Chan WCW, Maxwell DJ, Gao XH, Bailey RE, Han MY, Nie SM 2002 Luminescent quantum dots for multiplexed biological detection and imaging. Current Opinion in Biotechnology 13(1):40-46.

2. Alivisatos A, Gu W, Larabell C 2005 Quantum Dots as Cellular Probes. Annual Review of Biomedical Engineering 7:55-76.

3. Murray C, Kagan C, Bawendi M 2000 Synthesis and characterization of monodisperse nanocrystals and close-packed nanocrystal assemblies. Annual Review of Materials Science 30:545-610.

4. Alivisatos AP 1996 Semiconductor clusters, nanocrystals, and quantum dots. Science 271(5251):933-937.