中孔結構之二氧化矽奈米材料在生物上的應用

Mesostructured Silica Nanoparticles: Biological Applications

張豐鵬(Feng-Peng Chang)

指導教授 ： 牟中原

國立臺灣大學/理學院/化學研究所/博士(2014年)

https://doi.org/10.6342/NTU.2014.11141

摘要

中孔洞奈米矽材泛指具有 2-50 nm 孔洞結構之二氧化矽奈米材料。因為具有高的表面積與孔洞特性 ，此材料在奈米生醫領域中吸引廣泛的注意與應用。最近，一種二氧化矽相似材料(Cornell dots)已經進入人體臨床實驗。這是個令人振奮的消息，它鼓舞我們對中孔洞奈米矽材做進一步地研究與改善，並期待能將此材料推向市場應用端。本論文共包含了五個章節，內容專注於中孔洞二氧化矽奈米材料的合成、結構鑑定、表面修飾、與其在生物上的應用。
第一章節為中孔洞奈米矽材概論，內容描述規則中孔洞與空心結構之中孔洞二氧化矽奈米材料的合成方法、形成機制、生物相容性、與生物上的應用。
第二章節探討中孔洞奈米矽材應用於植物轉殖工程的可行性。在此研究領域，我們有相當突破性的進展。研究發現，中孔洞材料可以不需藉由任何外力自發性地攜帶 DNA 進入植物組織中。這對運送外來物質進入植物組織的研究會有顯著的發展。
第三章節報導一種將酵素包覆於空心奈米球的新穎方法。此奈米空心球具有可讓物質自由通透的孔洞結構。進入細胞後可在細胞中進行酵素的催化反應並達成癌症治療目的。
第四章節闡述人造胞器的概念。奈米空心球因為具有大的內部反應空間與通透性球殼，因此可以同時包覆多種酵素進行複雜的連續性反應。就像細胞內胞器一般，我們包覆多種酵素於奈米空心球中，並期待此人造胞器與細胞結合後可以發展成具有醫療價值的工具。
第五章節總結了所有的研究工作，同時對於未來研究提出個人看法與展望。

關鍵字

孔洞結構二氧化矽奈米材料 ； 基因轉殖 ； 蛋白質輸送 ； 奈米反應器 ； 人造胞器.

並列摘要

Mesoporous silica is a form of silica with a pore diameter from 2 to 50 nm. Due to their high surface area and pore structure, Mesostructured silica nanoparticles (MS-NPs)have drawn with extensive attentions in biotechnology applications. Recently,multimodal silica nanoparticles (Cornell dots),a kind of silica materials, have been approved for a first-in-human clinical trial which inspires and brings us to work on the subjects to improve and optimize the MS-NP-based materials for commercial purposes.
There are five chapters in this dissertation which focuses on the synthesis, chemical and physical characterization, surface functionalization, and biological applications of
MS-NPs.
In Chapter 1, I described the general introduction of MS-NPs, including the preparation of ordered/hollow-type mesoporous silica nanoparticles, the formation mechanism, biocompatibility, and biological applications.
In Chapter 2, I explored the possibilities of using mesoporous silica nanoparticles (MSNs) in plant bioengineering. This study is pioneer of introducing biomaterials into intact plants without the aid of any mechanical force and has significant applications in multi-cargo delivery.
In Chapter 3, I reported a novel method of entrapping enzymes inside hollow-type MSNs (HMSNs). The enzyme-filled nanoparticles allowing transport of substrates and products were delivered into cancer cells. The idea is to have a nano-sized catalytic reactor functioning inside living cells for therapeutic purpose.
In Chapter 4, I proposed the concept of “artificial organelles.” Like a bio-compartment mimic, the special architectures of HMSNs with an interior reaction space and substrate-permeable shells could load multiple enzymes to process cascade reactions. This idea raised the possibility of artificial organelles to enhance the cell metabolic ability in either increasing life-span or cell fate for the medical use.
In Chapter 5, I summarized my research works, opinions and future directions of studies.

並列關鍵字

mesostructured silica nanoparticles ； gene transformation ； protein delivery ； nanoreactors ； artificial organelles.

參考文獻

Section 1:

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(2) Kresge, C. T.; Leonowicz, M. E.; Roth, W. J.; Vartuli, J. C.; Beck, J. S. Ordered Mesoporous Molecular-Sieves Synthesized by a Liquid-Crystal Template Mechanism. Nature 1992, 359, 710-712.

(3)Tang, F. Q.; Li, L. L.; Chen, D. Mesoporous Silica Nanoparticles: Synthesis, Biocompatibility and Drug Delivery. Adv. Mater. 2012, 24, 1504-1534.

(4) Kwon, S.; Singh, R. K.; Perez, R. A.; Abou Neel, E. A.; Kim, H. W.; Chrzanowski, W. Silica-Based Mesoporous Nanoparticles for Controlled Drug Delivery. J. Tissue Eng.