摘要:傳統技術將層狀黏土改質為不規則脫層型黏土需經兩個步驟,而本計畫共同主持人
林江珍教授所研發出的新型黏土脫層劑僅需一個步驟就能使雲母與蒙脫土等層狀黏土
成為脫層形式的無機黏土,藉由此高分子型界面活性劑將多層狀黏土脫層為奈米矽片
(NSP),其微觀結構約為100×100×1 nm3 薄片狀,片片皆獨立存在,具有高電荷,能穩
定分散於水與有機溶液中。進一步以聚乙烯醇(或脂肪胺鹽)修飾後,延伸出可操縱親水
或親油性之矽片(NSQ),且可與高分子形成奈米複合材料;而使用不同的黏土作為分散
劑吸附奈米銀粒子,又可形成奈米銀脫層黏土(AgNPs/NSP)。以上一系列NSP 衍生物
(NSP, AgNPs/NSP, NSQ, AgNPs/NSQ)均具有高分散性、高離子負電荷性、特殊幾何特性
與有機親和性及自組裝之特性,可由一級結構自組裝成為二級及三級形態,且均可與生
醫材料混摻製成薄膜材料。在計畫主持人徐善慧教授初步的研究中發現,奈米矽片幾乎
沒有細胞毒性,經混摻至聚胺酯後可大幅提升牛頸動脈內皮細胞貼附及生長。此外,也
發現經高分子包覆的奈米矽片仍具有抗菌性,其機制有待深入探討,未來也可衍生出以
高分子作為奈米矽片載體,以降低奈米材料毒性並提高其生醫應用。
本計畫擬對此一系列新穎之無機奈米脫層黏土材料進行更深入的探討與研究。將分
別從細胞相容性、抗微生物及抗病毒三個方面著手,瞭解這些新穎奈米材料與組織細胞
/微生物細胞間之交互作用,而進一步確立在生醫應用上之潛力。首先由林江珍老師製備
並研發不同的奈米矽片衍生物,由徐善慧教授針對獨立的矽片或與生醫高分子聚胺酯形
成的奈米複合材料,與細胞(巨噬細胞、纖維母細胞、內皮細胞及間葉幹細胞)之間的交
互作用與分子機制進行探討,並確定其安全性。在抗菌機制上,蘇鴻麟教授先前已發現
AgNPs/NSP 於低濃度下即可抑制多重抗藥性菌株金黃色葡萄球菌、包氏不動桿菌等多種
細菌生長,將繼續探討其抗菌機制。在抗病毒潛力的開發上,林宜玲教授也證實病毒感
染時,加入奈米矽片可抑制數種病毒的複製,由於奈米矽片表面具有高電荷,可能導致
蛋白質變性,而降低病毒的感染力;奈米矽片與luciferase 結合後,酵素活性大為下降,
也間接證實此一觀點,未來將繼續探討其抗病毒之機制與體內抗病毒之能力。綜合以上
所述,經由四位不同專長學者的跨領域結合,期望將新穎之奈米矽片材料應用於生醫材
料與抑制微生物生長上。
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Abstract: Recently, one of the team members in this proposed project has developed a one-step
process using polyamine surfactants to delaminate layered silicate clay into random nano
silicate platelets (NSP). Owing to the presence of high surface area (average dimensions of
100×100×1 nm3) and intensive charge density (ca. 20,000 ions per platelet), the randomized
NSP were shown to have unique properties when interacting with polar organics as well as
biomaterials. Our preliminary studies indicated that our newly developed NSP had unexpected
efficacies of inhibiting bacterial growth and dengue virus infection, interfering with the DNA
replication and the process of polymerase chain reaction, absorbing UV light and
self-assembling to films of self-cleaning. In addition, our preliminary results showed that this
newly developed nanobiomaterial had very low toxic effect and elicited only minor
inflammatory responses in our in vitro cell culture and in vivo animal models. Thus, our
newly developed NSP have great potentials to be developed for a variety of biomedical
applications, including anti-virus, anti-microbes as well as biomaterials (used alone or as
nanocomposites).
In this proposal, we will explore the chemical and physical properties of NSP by further
modifying with hydrophobic and hydrophilic organics, including fatty amine and
polyethylene glycol to tailor their functionalities. We will also study the silicate
platelet-organic hybrids and those carry AgNPs so as to understand the specific properties and
interaction with cells. With different properties, NSP derivatives can be made into polymer
composites (films). The polymer serves as carrier of NSP derivatives and further reduces their
risks. The polymer selected in this study is polyurethane (PU). PU is not only popular as
biomaterials, but also has an intrinsic nanostructure, which can be modified by the addition of
(extrinsic) nanomaterials such as NSP. This makes PU-NSP nanocomposites unique among all
polymer nanocomposites. Comprehensive technologies and expertise in the areas of
nanomaterials, cell and molecular biology, virology, immunology, and biomaterials will be
included to tackle these problems, particularly for elucidating the mechanisms of
nanomaterial-biosystem interactions. The proposed project aims at development of newly
invented NSP for biomedical applications, particularly as biomaterials or to control microbial
and viral infections, and elucidation of the underlying mechanisms. It is expected that many
practical applications will be established. Efforts on the screening the effectiveness of NSP
and its derivatives will be initiated after establishing the methodology of functionalizing NSP
for specificity as well as determining the mechanistic insights of NSP/cell (microbe)
interactions. Our team members consist of multidisciplinary outstanding researchers,
including expertise in various fields such as those mentioned. The team members are able
investigators who are determined to go beyond the conventional paradigms and work together
to achieve our goals. We believe this proposal will also broaden the mechanistic view on the
interaction of nanomaterials with cells and the biological system in molecular level,
ultimately bringing up the academic excellence and creating a host of biomedical applications.