2009-02-012024-05-15https://scholars.lib.ntu.edu.tw/handle/123456789/665652摘要:本研究三年計畫將著重於合成具有生物相容性及可控制的粒子形態及表面官能性的中孔徑氧化矽奈米材料 (mesoporous silica nanomaterials; MSNs),並且用於細胞內的藥物傳遞及控制釋放等生醫應用。在第一年內,我們將致力於合成中孔徑氧化矽奈米材料並且探討導入的有機官能基如何影響其產物MSN的孔徑結構與粒子形態。在第二年內,我們將會利用共聚合 (Co-condensation) 和 嫁接 (Grafting) 方法將有機官能基加入中孔徑氧化矽奈米材料的管壁中,藉此提供孔洞一種以非共價鍵的相互作用的方式來控制藥物,胺基酸,蛋白質及核酸。我們也會提出一種以聚離胺基酸 (Poly-lysine) 做為蓋子的新型覆蓋/去覆蓋式MSN材料做為藥物的載體並期望此載體在進入細胞前不會有漏出的現象 (premature release)。第三年時,我們計劃系統性地研究MSN和細胞之間的相互作用。這些作用包括了:(1) 細胞膜對MSN的吸附,(2) 材料進入細胞的機制和動力學,(3) MSN的生物相容性及在細胞內的位置,(4) MSN對細胞新陳代謝的影響。 本研究計畫為一個無機化學,有機合成,細胞生物學的創新結合,因此對於無論是基礎研究及實際應用皆非常重要。我們預期這項利用中孔徑氧化矽奈米材料做為藥物載體在生物及生醫應用的研究工作將提供給材料科學家與化學家一種創新設計概念。同時這項跨領域的研究也會讓從事此計劃的學生得到許多的訓練及學習。 <br> Abstract: This three-year research proposal is focused on the synthesis of biocompatible mesoporous silica nanomaterials (MSNs) with desired particle morphologies and surface functionalities and the bio-applications of these materials in intracellular delivery and controlled release. In the first year, we will focus on the synthesis of MSNs and on the study of how the organic functionality affects the mesoporous structure and particle morphology. In the second year, we will functionalize the mesoporous surface with different organic groups by co-condensation and grafting methods to offer a variety of non-covalent interactions for the control of loading of diverse molecules including drugs, peptides, proteins, and nucleotides. A new capping/uncapping MSN-based system by using poly-lysine as a gatekeeper will also be performed in order to achieve zero premature release. In the third year, we plan to systematically study various interactions between MSNs and animal cells, and the interactions include: (1) the adsorption of MSN to cell membranes, (2) the mechanism and kinetics of internalization, (3) the biocompatibility, the intracellular localization of MSN, and (4) the effects of MSN on cellular metabolism. This research work represents an innovative combination of inorganic materials, organic synthesis, and cell biology, which is very significant for both fundamental study and practical application. We envision that this work will offer a new design principle for material scientists and chemists to fully take advantage of the mesoporous structures as scaffolds for fabrication of a new generation of nanodevices for the biological and biomedical applications. The highly interdisciplinary nature of this project will also give valuable training to the students that will be working on this work.中孔徑奈米材料細胞傳遞與釋放控制共聚及嫁接法氧化矽奈米粒Mesoporous materialsintracellular delivery and controlled releaseco-condensation and grafting methodsSilica nanoparticles設計與合成高規則結構的多功能中孔徑氧化矽奈米材料並應用於細胞內的藥物傳遞與控制釋放