基于"分子阀门"的硫化银量子点/介孔硅可控释放系统用于靶向基因和药物共转运的实时示踪研究

The targeting controlled release system based on silver sulfide quantum dots / mesoporous silica nanoparticles with molecular valve is used to real-time tracking the co-delivery of gene and drug targeting research. The basic idea is, after loading anticancer drug in the mesoporous silica nanoparticles, molecular valve responsing tumor characteristics stimulation signal is installed, targeting ligands and near infrared non-toxic silver sulfide quantum dots coated with silence siRNA to multidrug resistance gene of tumor cells are respectively connected to the nanocarrier; the functional nanocarrier can transport drug to the site of the tumor initiatively, at the same time, silence the multidrug resistance related gene in tumor cell, reverse multidrug resistance phenomenon; in pancreatic cancer animal model, based on the "molecular valves" silver sulfide quantum dots / mesoporous silicon controlled release system, carry out the targeted drug and gene co-transport of real-time tracing study. The silver sulfide quantum dots in the load of siRNA also can be used as fluorescent probes in real time dynamic tracing nanocarriers to transport in the body of the target. The study is expected to provide important technical means for collaborative treatment of drug and gene, provide an important support for the biological process of a comprehensive understanding of gene and drug treatment, and provide a theoretical basis and effective new method and technology for comprehensive prevention and treatment of tumor, has the important research value.

本项目拟构建基于"分子阀门"的可同时转运药物和基因的硫化银量子点/介孔硅纳米靶向可控释放系统，开展基因和药物靶向共转运的实时示踪研究。基本思路是在介孔硅纳米材料装载抗癌药物后"安装"能响应肿瘤特征刺激信号的"分子阀门"，将靶向配体和负载有能沉默肿瘤细胞多药耐药基因siRNA的近红外无毒硫化银量子点连接到纳米载体上,经此构建的功能化纳米载体在将化疗药物主动输送到肿瘤部位的同时可沉默肿瘤细胞的多药耐药相关基因，增强抗肿瘤效果；之后以胰腺癌小动物为模型，开展基于"分子阀门"的硫化银量子点/介孔硅可控释放系统用于靶向基因和药物共转运的实时示踪研究；其中硫化银量子点在负载siRNA的同时还可作为荧光探针实时在体动态示踪纳米载体在体内的靶向转运过程。该研究有望为药物和基因的协同治疗提供重要的技术手段，为全面理解基因和药物协同治疗的生物学过程提供重要的支撑，为肿瘤综合防治提供理论依据和有效的新技术新方法

本项目通过构建基于“分子阀门”的可同时转运药物和基因的硫化银量子点/介孔硅纳米靶向可控释放系统，开展基因和药物靶向共转运的实时示踪研究，用于肿瘤的治疗。基本思路是在介孔硅纳米材料装载抗癌药物后“安装”能响应肿瘤特征刺激信号的“分子阀门”，将靶向配体和负载有能沉默肿瘤细胞多药耐药基因siRNA的近红外无毒硫化银量子点连接到纳米载体上,经此构建的功能化纳米载体在将化疗药物主动输送到肿瘤部位的同时可沉默肿瘤细胞的多药耐药相关基因，增强抗肿瘤效果；之后以肿瘤小动物为模型，开展基于“分子阀门”的硫化银量子点/介孔硅可控释放系统用于靶向基因和药物共转运的实时示踪研究；其中硫化银量子点在负载siRNA的同时还可作为荧光探针实时在体动态示踪纳米载体在体内的靶向转运过程。该研究为药物和基因的协同治疗提供了重要的技术手段，为全面理解基因和药物协同治疗的生物学过程提供重要的支撑，为肿瘤综合防治提供理论依据和有效的新技术新方法。项目原预期在国际SCI 收录权威期刊发表论著8-10篇，其中影响因子大于5的3-5篇,申请国家发明专利1-2项；实际发表SCI论文37篇（影响因子大于5的有19篇），并申请国家发明专利2项另授权国家发明专利1项，在成果方面超出了最初的计划。