siRNA是RNA干扰过程的常用工具，可靶向沉默特定基因，在癌症治疗、细胞凋亡调节、血管生成调控、疾病相关基因筛查、药物靶标寻找等方面具有重要应用。使用纳米材料负载siRNA是有效完成siRNA体内递送的重要手段。纳米材料的常规制备方法具有步骤繁琐、条件不易控制、仪器需求种类多等不足。为了提升合成条件的可控性以及提高合成装置的集成性，本项目拟采用微流控芯片技术实现siRNA负载纳米颗粒的自动合成。通过设计制造多入口多级的集成化微流控芯片，实现磷脂-PLGA-磷脂-siRNA分子的多级自组装，整合脂质体和PLGA纳米颗粒的优点，制备具有缓释、靶向、安全、可降解、高负载、高活性等性质的siRNA负载纳米颗粒。并通过对颗粒性能和生物效应的评价与研究，选择最优的合成条件，充分发挥微流控芯片高度集成化和流体精确可控的优势，建立siRNA负载纳米颗粒的高效自动化合成方法。

siRNA, the important tool for RNA interference process, can achieve specific gene silencing and has many novel applications in cancer treatment, regulation of cell apoptosis, and screening of disease-related gene and drug targets. Nanomaterials are one of the most used carriers for in vivo siRNA delivery. Conventional methods for preparing siRNA-loaded nanoparticles involve complicated procedures, lack of condition control, and require expensive instruments. To address these challenges, microfluidic platforms have been employed for controlled generation of siRNA-loaded hybrid nanoparticles. The microfluidic chip is composed of multi-stages to form the multilayer structure of lipid-PLGA-lipid-siRNA nanoparticles by self assembly. The generated siRNA hybrid nanoparticles integrate the advantages of liposomes and PLGA nanoparticles, with great properties of slow-release, targeting, safety, biodegradability, high loading efficiency and high activity. Through the evaluation and study of the properties and biological effects of the hybrid nanoparticles, the optimal microfluidic synthesis conditions will be investigated.