超声微泡造影剂在体内的稳定性、声学特性及成膜材料的界面性质直接影响基因递送和转染效率。寻找一种理想的基因载体，安全高效的将目的基因导入靶细胞是超声微泡介导基因递送和转染的关键，也是基因治疗的前提条件。天然丝素蛋白以其良好的生物相容性及良好的力学性能被广泛用于组织工程领域，同时其表面的活性氨基酸残基位点利于细胞的黏附和基因转染。基于此，本项目利用同轴静电电喷技术，以丝素蛋白为外壳材料构建新型丝素蛋白超声微泡造影剂；同时基于微泡载体在肿瘤组织内的传质过程，结合肿瘤生物学、超声影像学、力生物学等综合学科的研究方法及技术，建立新型含内皮细胞层、肿瘤细胞层的共培养模型。从离体水平和在体水平考察微泡载体的稳定性、声学特性、与靶细胞的黏附性及基因转染率。本项目旨在构建新型超声造影剂，既能增强基因转染率实现靶向治疗又能特异性显影实现分子影像的诊断目的。

The properties of microbubble ultrasound contrast agents such as the stability in vivo,the acoustic and interface properties of shell materials have a great effect on gene delivery and transfection efficiency. It is important to find an ideal gene carrier to direct gene transfer into target cells safely and efficiently, which is also a prerequisite for gene therapy. It is well known that silk fibroin from natural silkworm cocoon have good biocompatibility and mechanical properties and have been widely used in the field of tissue engineering. The active surface amino acid residues of silk fibroin are benefited for cell adhesion and gene transfection. Based on this, a novel ultrasound contrast agent is designed and fabricated by coaxial electrosrpay technology and silk fibroin are been used as shell material. Meanwhile this project also establishes a new co-culture model with endothelial cells layer and cancer cells layer through an interdisciplinary combination of approaches that includes tumor biology, stress biology and ultrasound molecular imaging. The stability and acoustic characteristic of ultrasound contrast agents and target cell adhesion and gene transfection are investigated in vitro and in vivo. The project may provide meaningful design considerations for microbubble ultrasound contrast agents fabrication and the gene transfection efficiency may be enhanced and the tumor diagnosis and gene therapy purposes can be fulfilled.