可去PEG屏蔽的还原敏感型化疗药物与siRNA的共运输纳米载体的构建及评价

项目名称： 可去PEG屏蔽的还原敏感型化疗药物与siRNA的共运输纳米载体的构建及评价

项目编号： No.51303120

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 一般工业技术

项目作者： 朱彩虹

作者单位： 苏州大学

项目金额： 25万元

中文摘要： 骨肉瘤的治疗是目前骨科学界非常棘手的难题，而将化疗药物和siRNA包裹于同一纳米粒，可达到协同增效的效果，这为骨肉瘤的联合治疗提供了新的思路。但目前报道的大部分共运输载体仍局限于在细胞层面的应用，需提高载体在细胞外的稳定性和实现药物与siRNA在细胞内的快速释放。我们在前期研究中发现，能响应细胞内还原环境去PEG屏蔽和快速还原降解的药物或基因载体可使载体在生理盐环境中稳定以及能实现药物或基因在细胞内的快速释放。因此，本项目拟通过聚氨酯方便的结构可设计性，以可还原降解的聚碳酸酯为二醇和胱胺封端的PEG为扩链剂，通过赖氨酸二异氰酸酯接枝短链PEI后,可获得一种在细胞内还原环境下可去PEG屏蔽的和快速还原降解的、能同时装载药物和siRNA的共运输纳米载体，有望使载体在细胞外稳定和实现药物和siRNA在细胞内的快速释放，为骨肉瘤的药物与siRNA的共载治疗在体内的高效应用提供一种新的载体与思路。

中文关键词： 聚氨酯；还原敏感；骨肉瘤；；

英文摘要： The therapy of oesteosarcoma is always a tricle problem in orthopedics.In recent years, simultaneous delivery of siRNA and chemotherapeutics to cancer cells has been approved to achieve synergistic/combined effect in cancer therapy,which would show great application respect in osteosarcoma therapy. However,most of the reported codelivery nanoparticles were used only in cells not in vivo. Because when being used in vivo, a series of extracellular and intracellular obstacles should be overcomed before the vehicle can release its payloads at the desired site, especially to improve the stability in extracellular environment and controlled intracellular release. Based on our previous research, we found that reduction-responsive nanocarriers for drug or gene delivery have received can fast release their cargo in redox intracellular environment by the way of PEG de-shielding or by the way of fast reductive degradation. So, we want to design a reduction-responsive nanocarrier for codelivery of drug and siRNA to overcome the multidrug-resistance of osteosarcoma in vivo.The nanocarries can be long-time circuling in vivo, while the carriers would be PEG de-shielded and further fast degraded in redox intracellular environment.So,the drug and siRNA could been fast triggered release,which would induce improved synergistic ef

英文关键词： polyurethane；reducible；osteosarcoma；；