基于Con A门控分子的甘露糖响应型介孔二氧化硅纳米控制释放体系  

A mannose-responsive controlled-release system based on Con A-gated mesoporous silica nanocontainers

作　　者：罗洁蓉 邹振[1] 何晓晓[1] 王柯敏[1,2] 何定庚[2] 杨雪[1] 李学财 蒋晓春[1] 

机构地区：[1]湖南大学生物学院化学生物传感与计量学国家重点实验室生物纳米与分子工程湖南省重点实验室,长沙410082 [2]湖南大学化学化工学院,长沙410082

出　　处：《科学通报》2014年第18期1707-1714,共8页Chinese Science Bulletin

基　　金：国家自然科学基金(21190044,21175039,21322509,21305035,21305038,21190044,21221003);湖南省科技计划(2012TT1003);国家大学生创新性实验计划(201210532075)资助

摘　　要：选择凝集素伴刀豆球蛋白A(Con A)作为门控分子,利用甘露糖和葡萄糖与Con A竞争性结合的特性,构建了一种新型的Con A封堵介孔二氧化硅(MSN)的甘露糖刺激响应型控制释放体系.在该体系中,氨基葡萄糖首先与氰酰基修饰的MSN交联合成表面葡萄糖功能化的MSN,然后通过葡萄糖与Con A的多价结合作用使Con A固定到MSN表面,封堵介孔,形成Con A封堵MSN的甘露糖刺激响应型控制释放体系(MSN-Glc-Con A).利用电子显微镜、热重分析、X射线衍射、红外光谱和比表面积分析等手段表征了该纳米控制释放体系的制备过程,并且以联钌吡啶染料分子作为模式客体分子,研究了模式客体分子在该体系中的包裹及甘露糖调控下的刺激响应释放行为.实验结果表明,该体系具有较高的包载量(89.90±7.73μmol/g SiO2)和良好的甘露糖刺激响应释放行为.在没有甘露糖存在时,Con A能有效封堵介孔,使包载的染料分子几乎无释放;在甘露糖存在的条件下,甘露糖与Con A发生竞争性结合,Con A从MSN表面脱离,介孔打开,染料分子释放.染料分子的释放率呈浓度依赖性和时间依赖性,在40 mmol/L甘露糖的条件下,340 min内染料分子释放率超过90%.该体系是一种理想的糖刺激响应控制释放载体,有望实现在药物运输领域的应用.In this work, a novel delivery system based on Concanavalon A（Con A）-gated glucose-functionalized mesoporous silica nanoparticle （MSN-Glc-Con A） was constructed for the mannose-responsive controlled release. In this system, glucose was firstly modified on the surface of mesoporous silica nanoparticles （MSN） through the crosslinking reaction between glucosamine and cyanato-functionalized MSN. Con A, a lectin, was subsequently bound the functionalized glucose epitopes through multivalent carbohydrate- protein interactions, resulting in blockage of pores and inhibition of guest molecules release. In the presence of mannose, the Con A competitively bound with mannose and got away from the pore of MSN because of higher affinity for mannose. Thus, the pores were uncapped and the entrapped guest molecules were released. The physical and chemical properties of the as-synthesized MSN were characterized by transmission electron microscopy, X-ray diffraction, Fourier transform Infrared spectroscopy, Brunauer-Emmett- Teller and thermogravimetric analysis. As a proof-of-principle, [Ru（bipy）3]C12 was selected as the model guest molecules, and the mannose-responsive loading and release of [Ru（bipy）3]C12 have been investigated. The results demonstrate that the system had excellent loading amount （89.90 ±7.73μmol/g SiO2） and good mannose-responsive release behavior. Release-profile studies in MOPS buffer showed that no [Ru（bipy）3]Cl2 leaked when the pore was closed and that release occurred immediately after adding mannose. The dye release percentage can over 90% after treatment with 40 mmol/L mannose for 340 min. This lectin-gated MSN delivery system is a promising candidate for therapeutic agent delivery.

关 键 词：伴刀豆球蛋白 甘露糖 竞争性结合 介孔二氧化硅 控制释放 

分 类 号：TQ127.2[化学工程—无机化工]