本研究主要是以二氧化矽奈米粒子的表面改質,製備nitric oxide (NO)遞送系統。利用二氧化矽奈米粒子表面的矽烷醇基與 4-Isocyanato-4’(3,3-dimethyl-2,4-dioxo-azetidino) diphenyl methane (MIA) 上的 isocyanate官能基具有的高反應性,成功將二氧化矽奈米粒子表面化學官能基化,並命名為SIA。之後分為兩種合成方式,其一是利用改質後的SIA具 azetidine-2,4-dione官能基,可將具胺官能基的chitosan (CS) 接枝於二氧化矽奈米粒子表面,再與thioglycolic acid (TGA) 反應,成功將thiol接枝於二氧化矽奈米粒子表面,命名為SCSH。 另一種方法,則是利用一級胺與羧酸的良好反應性,將CS與TGA反應為CT,再與SIA的azetidine-2,4-dione官能基反應,亦成功將thiol接枝於二氧化矽奈米粒子表面,命名為SCT。SCSH及SCT上的thiol經亞硝基化反應,可形成具有NO釋放功能的硫-亞硝基硫醇化二氧化矽奈米粒子,分別命名為SCSNO及SCTNO。 所形成的二氧化矽奈米粒子,可由FT-IR、ESCA、SLS、SEM、TEM鑑定其結構,並以TGA、Ellman assay、Griess assay做定量分析,測定其thiol含量及NO載量。其中每mg的SCSNO可攜帶0.08 μmol的NO,每mg的SCTNO則可攜帶0.17 μmol的NO,成功以新的合成方式製備具NO釋放能力的二氧化矽奈米粒子。
The subject of this study is to develop a novel approach to synthesize functional silica nanoparticles which have the abilities of NO storage and controlled release via RSNOs donor. The bifunctional reactive agent of 4- isocyanato- 4'-( 3,3'- dimethyl- 2, 4- dioxo- azetidino ) diphenyl methane (MIA) is employed to modify the surface of silica nanoparticles. Consequently, the isocyanate group of MIA reacts with silanol groups of silica nanoparticles while the azetidine-2,4-dione group of MIA demonstrates a high reactivity and selectivity with primary amine groups of chitosan. Furthermore, NO donors are formed by incorporation thiolglycolic acid into chitosan structure via exposed to acidified nitrite. Moreover, we also try the other different synthetic method by combining thiol group and chitosan first before amine group modifying silica nanoparticles. The chemical structures of nanoparticles are confirmed by FT-IR, ESCA, SLS, SEM, TEM. Additionally, we use Ellman assay to quantify the amount of thiol groups on modified silica nanoparticles, and the characterization of NO release is observed by Griess assay.The results presented here show that SCTNO particles can be more promising NO release system than SCSNO particles, the former demonstrate the NO storage of 0.17 μmol NO/ mg particle while the latter with 0.08 μmol NO/ mg particle.