【作者】 陈亮；

【导师】 王新灵；

【作者基本信息】 上海交通大学 ， 材料科学与工程， 2014， 硕士

【摘要】 本文以介孔硅纳米粒子为基体构建了一种新型还原响应性控释系统，控释系统的合成通过采用后改性法对介孔硅纳米粒子进行表面修饰完成。本文以两种不同类型的介孔硅纳米粒子SBA-15和MCM-41作为基体，分别获得了由L-胱氨酸二甲酯链接的mPEG包覆的有机功能化介孔硅纳米粒子；其中介孔硅纳米粒子作为客体分子的纳米储存器，而表面修饰的有机层则作为封堵介孔的纳米控制器。由于L-胱氨酸二甲酯分子中含有二硫键，能被细胞水平的谷胱甘肽还原成巯基而断开，包封在介孔中的客体分子就得以释放出来。介孔硅纳米粒子的有机功能化修饰已通过FTIR、固体核磁硅谱、元素分析和TGA等结构表征和组成测定方法得到证实。修饰后的介孔硅纳米粒子的介孔结构已通过TEM、SEM、XRD和氮吸附测试等进行表征，结果表明SBA-15和MCM-41均具有二维六方介孔结构，且随着有机部分的引入二者有序程度都有所降低，但前者比后者具有较大的孔径和较低的比表面积。此外，DLS测试证明mPEG修饰后的纳米粒子具有更好的水溶液稳定性，zeta电位测试表明它们均具有阴离子表面。用紫外可见光谱跟踪对比了载有荧光染料罗丹明B的两种功能化介孔硅纳米粒子在含有10mM谷胱甘肽和不含谷胱甘肽的PBS溶液中的释放行为。结果表明，在谷胱甘肽溶液中染料均能被快速释放，但两个控释系统具有不同的释放行为，基于SBA-15的控释系统表现为独特的逐步缓释行为，而基于MCM-41的控释系统则表现为突释行为。综合以上结果，本文所合成的有机功能化介孔硅纳米粒子是有效的药物控释材料，以不同类型介孔硅纳米粒子为基体的控释系统具有不同的释放行为，适合不同的给药要求，预期在生物医药领域有良好的应用前景。更多还原

【Abstract】 A unique redox responsive system for glutathione (GSH) triggeredcontrolled release was constructed based on mesoporous silicananoparticles (MSNs) in this study. The system was prepared by surfacemodification of the MSNs in the way of post-synthesis. Based on twotypes of MSNs, SBA-15and MCM-41, the corresponding systems wereobtained by modifying the MSNs with L-cystine ester linked mPEG chains,in which the former was served as the nanoreservoir of guest moleculesand the latter was applied as gatekeepers to block the mesopores. Thedisulfide-bond in L-cystine ester can be effectively cleaved by redoxreaction in the presence of GSH with a concentration at cancer cell level,and then the guests encapsulated in the pores were released.Chemical structure and composition of the functionalized MSNs wascharacterized by FTIR, TGA,29Si MAS NMR and EA and the resultsshowed that the MSNs were successfully modified by the organics. The mesoporous structure was analyzed by TEM, SEM, XRD and nitrogenadsorption. The results showed that both SBA-15and MCM-41possessevident2D-hexangonal mesostructure, which become less ordered with thegrafting of organic portions. Compared with MCM-41based MSNs,SBA-15based MSNs showed larger pore sizes and lower surface areas.Besides, DLS tests indicated that the introduction of mPEG enhancedstability of the MSNs in aqueous solution and an anionic surface of theMSNs was observed by zeta potential tests.Fluorescein dye as the model drug was loaded into the MSNs andreleased in PBS with10mM GSH and without GSH respectively to testthe controlled release properties of the MSNs using UV-Vis spectra as thedetector. The results showed that fluorescein dye in PBS with10mM GSHwas released much more rapidly. Moreover, a different release behaviorwas discovered when changing the MSN matrix. The SBA-15basedsystem showed a distinctive release behavior of steadily releasing whilethe MCM-41based system showed a burst effect followed by a very slowrelease. According to the results above, the MSNs synthesized from bothSBA-15and MCM-41can be used as an effective drug controlled releasesystem for biomedical applications, and the systems based on differentMSN matrix can meet different requirements of drug administration in practical application.更多还原