同步輻射X射線輔助合成奈米尺度之聚合物與粒子及其生物醫學研究上之應用

Synchrotron X-ray Assisted Synthesis of Nanoscale Polymers and Particles and Their Biomedical Applications

林峰賢(Fong-Sian Lin)

指導教授 ： 楊重熙 ； 曾繁根

國立清華大學/原子科學院/工程與系統科學系/博士(2013年)

https://doi.org/10.6843/NTHU.2013.00195

摘要

同步輻射X光是一具有高強度、高同調性及低發散性的光源，足以有效地引起許多的光化學反應，無論是使用於有機聚合物或是無機奈米粒子的合成都有不同於以往的成效。回顧文獻當中的聚合反應，傳統輻射化學和有機化學必須使用具有乙烯基的化合物做為單體(monomer)，再給予輻射能量或化學起始劑以誘發自由基而產生聚合反應，但由於同步輻射X光提供高達105 Gy s-1的劑量率，在我們研究當中發現可以對於僅含碳碳單鍵的單體進行聚合反應。使用含有胺基的單體(如：ethylenediamine, ethanolamine)合成含有linear-like polyethylenimine (LPEI)的聚合物或共聚物，可以被用來載送small interfering RNA (siRNA)進行RNA interference (RNAi)用於癌症治療，無論是在細胞層次或是活體動物實驗都有不錯的成效。另一研究，使用ethylene glycol單體以輻射合成non-linear polyethylene glycol (NLPEG)，當NLPEG被修飾於基材表面時，提供相較於LPEG更緻密的保護層避免蛋白質吸附，可以應用於經常接觸血液及生物質環境的醫學材料增加其耐用度及表現性。
另一方面，使用同步輻射X光於合成無機奈米粒子研究上，同步輻射可以有效地光解水分子產生具有還原力的水合電子(solvated electron)及氫自由基，在適合的條件下還原金離子而形成奈米尺度粒子。同步輻射X光還原金離子的過程中輔以阿拉伯膠，由於阿拉伯膠分子具有孔洞，可以限制金奈米粒子成長而得到約2奈米的金奈米粒子，進一步地將金奈米粒子以中子活化後形成放射性奈米金粒子並應用於抑制腫瘤生長，此放射性粒子無論是以血液注射或是腫瘤處注射皆可以抑制腫瘤生長，並且隨時間可以逐漸地被排出體外避免長期累積而可能造成的生物毒性，是一個有潛力用於癌症治療的奈米材料。另一研究，使用矽奈米球做為輔助金奈米粒子合成的模板，由於同步輻射還原過程中不需加入任何化學穩定劑，所以在矽奈米球表面形成的金奈米粒子是不具任何化學修飾物；因此針對研究需求可以進一步地修飾特定化學物質於金奈米粒子表面，同時使金奈米粒子脫附至溶液當中，此法可以得到更緻密的化學修飾層而提升金奈米特性。
同步輻射X光應用於合成有機聚合物與無機奈米粒子，僅需數分鐘的反應即可完成，而且獲得的材料有更具以往優異的性質表現，是一值得繼續深入研究的科技與領域。

關鍵字

同步輻射 ； 光化學 ； 聚合物 ； 金奈米粒子

並列摘要

Synchrotron X-ray is an intense and coherent radiation, which can efficiently induce radiation-chemical reactions. In this thesis, we evaluated the use of synchrotron X-ray for synthesizing polymers and nanoparticles and applying the resulting products to biomedical studies.
Synchrotron X-ray is a promising radiation to polymerize alkane compounds. Polymerization of alkane does not commonly be observed in conventional polymerizations with radiations or chemical reagents. Linear-like polyethylenimine (LPEI) and linear-like polyethylenimine-co-polyethylene glycol (LPEI-co-PEG) were produced by irradiating the monomers of ethylenediamine and ethanolamine, respectively. The LPEI-based polymers were used to carry siRNAs for arresting cell cycle, silencing expression of green fluorescent protein (GFP) and suppressing tumor growth. Besides, ethylene glycol, another alkane monomer, was also polymerized to generate non-linear polyethylene glycol (NLPEG). The NLPEG was further modified onto a wafer and formed a compact layer for protein resistance that can be probably used on biomedical devices to increase durability and performance.
For synthesis of metal nanoparticles, synchrotron X-ray can induce water radiolysis and generate reducing species, such as solvated electron and hydrogen radical, which can reduce metal ions to nanoparticles with a suitable ligand or template in aqueous solution. First, gum arabic (GA) was used as a template to assist synthesizing a nanocomposite of GA-protected gold nanoparticles (AuNPs@GA). Because gum arabic is a branched polysaccharide with porous structure, the growth of gold nanoparticles is limited by reducing insufficient gold ions in the structure. The nanocomposite of AuNPs@GA was subsequently activated by neutron flux and formed radioactive 198AuNPs@GA for tumor suppression. The tumor growth was significantly suppressed via intravenous injection or intratumoral injection of 198AuNPs@GA. After the treatment, AuNPs were gradually excreted from the body that prevents potential toxicity of long-term nanoparticle accumulation. In the other study, silica nanoparitcle was used as a stabilizing template to synthesize bare AuNPs on the surface without any other chemical ligands. The bare AuNPs synthesized on silica nanoparitcle were easy for HS-PEG modification and subsequently released from template surface to solution. The Pegylated AuNPs from silica template were further proved a higher PEG coverage on the AuNP surface, comparing the AuNPs from citrate reduction and stabilization. This synthetic approach is potential to produce superior AuNP with the high ligand density.
Synchrotron X-ray is powerful radiation for synthesis of polymers and nanoparticles with good functionality in a few minutes, and is possible to carry out reactions and products that are still not discovered. Synchrotron X-ray assisted synthesis of nanoscale materials is worth further study.

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