构建安全高效的RNAi载体是RNAi疗法治疗基因型等重大疾病临床应用的关键之一。前期研究发现：作为RNAi载体，凝胶多糖curdlan及其功能化衍生物的纳米微球，能够有效在体传送siRNA，成功诱导RNAi，显著下调靶标mRNA的表达；然而此类纳米载体存在着功能化修饰与负载能力以及氨基化程度与毒性相矛盾的问题。本项目尝试避开直接氨基化curdlan的方法，拟通过快捷有效的click反应，一次性按比例对curdlan可控引入siRNA的结合功能基团、靶向功能化基团、有效保护及稳定基团，构建优化出新型高效的siRNA靶向纳米载体。本项目所开发的curdlan纳米载体有望克服siRNA负载容量与功能化修饰相矛盾的问题，并为RNAi 临床应用载体的开发提供一些理论依据和实际范例。

Construction of the novel effective carriers is a key to clinical application of RNAi for remedying critical diseases such as cancer. As the RNAi carriers, the nanoparticles made from cationic amino-curdlan and its functionalized derivatives, were able to deliver siRNA in vitro and vivo efficiently, that could induce RNAi to down-regulate targeted mRNA successfully. However, there are two major problems about such nanocarrier. The one is loading capacity of carriers conflicting with functionalization modification. Another is the contrariety of amination degree to toxicity. Inhere, we want to avoid using amination method to prepare the nanocarriers. In addition, targeting group, stabilizing group, and protecting group would be introduced to carriers in appropriated proportion at a time by click reaction. The nanocarrier of curdlan would be the promising candidate for resolving the contradiction between loading capacity and functionalization, which would also provide some theoretical and practical examples for developing carriers used on the RNAi application.