蛋白和核酸门控的新型介孔氧化硅输送体系的构筑及其控制释放性能

项目名称： 蛋白和核酸门控的新型介孔氧化硅输送体系的构筑及其控制释放性能

项目编号： No.21273112

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 杜学忠

作者单位： 南京大学

项目金额： 80万元

中文摘要： 药物靶向输送和控制释放是提高给药疗效、减少药物用量及其毒副作用的关键。影响给药疗效和细胞毒性的两个最重要条件是药物零提前释放及刺激响应控制释放。生物相容性介孔氧化硅具有的独特孔道结构和易表面功能化性质，被认为是智能控释给药最有前途的药物纳米容器和理想的载体材料。生物大分子门控的介孔氧化硅药物输送系统及其控制释放引起人们的极大关注。基于许多生物过程中配体与蛋白受体的多重相互作用以及药物分子与双链DNA嵌插结合作用模式，集纳米技术、自组装技术、生物识别和控制释放于一体，本项目提出构筑蛋白（凝集素蛋白和富含组氨酸蛋白）和核酸门控的新型介孔氧化硅控释体系，调控介孔氧化硅表面自组装甘露糖和亚胺二乙酸功能配体以及DNA嵌插基团的表面密度和空间分布，增强生物大分子结合亲和性。通过降低pH和生物分子竞争结合以及还原连接嵌插基团的二硫键，实现生理条件的刺激响应控制释放。推动介孔氧化硅药物输送系统的生物应用。

中文关键词： 介孔氧化硅纳米粒子；纳米载药体系；刺激响应；药物控制释放；肿瘤治疗

英文摘要： Controlled release of targeted drug delivery systems is to improve therapeutic efficacy and reduce amounts of drugs and their side effects. Zero premature release and stimuli-responsive controlled release of pharmaceutical cargos are two very important prerequisites that impact the therapeutic efficacy and cytotoxicity of drug delivery. Biocompatible mesoporous silica, with unique pore structure and ease of surface functionalization, is considered to be promising nanocarriers and ideal scaffolds for stimuli-responsive targeted drug delivery systems. Controlled release of biomacromolecule-gated mesoporous silica drug delivery systems has attracted much attention recently. Taking the advantage of the multivalent interactions between ligands and protein receptors in a variety of biological processes and the intercalative binding of drug molecules with double-stranded DNA, the project is to construct novel protein- (lectin and histidine-rich protein) and nucleic acid-gated mesoporous silica delivery systems in combination of nanotechnology, self-assembly, biomolecular recognition, and controlled release. Surface densities and spatial distribution of carbohydrate, and iminodiacetic acid, and DNA intercalator-functionalized mesoporous silica by self-assembly are regulated elaborately to enhance biomacromolecule bindin

英文关键词： mesoporous silica nanoparticles；nanoscale drug delivery systems；stimuli response；controlled drug release；tumor therapy