肿瘤是导致人类死亡的重要原因之一，对肿瘤的不懈研究以及治疗方法的探索一直是生命科学的焦点。近年来，靶向肿瘤的细菌载体作为一种新兴的治疗方法越来越多的受到关注。研究发现，细菌载体对于实体瘤的厌氧微环境具有特殊的靶向效应，但是机制并不清楚。我们通过前期研究，已构建出一株靶向肿瘤的减毒沙门氏菌细菌载体（YB1），建立了乳腺癌和原发肝癌的动物模型；并开始建立小动物活体成像平台，可以对细菌靶向肿瘤的整个过程进行实时监控。本项目拟研发多种兼容、稳定、以及组织穿透能力强的荧光蛋白，分别标记细菌和肿瘤细胞；从整体、局部和显微三个层面直接观测和记录细菌靶向肿瘤的全过程；研究在细菌治疗肿瘤过程中，细菌和肿瘤细胞、细菌和免疫细胞、肿瘤细胞和免疫细胞的相互作用。通过上述研究，力图阐明细菌靶向肿瘤的治疗中的作用机制，以及免疫系统在此过程中充当的角色，对于肿瘤的基础研究、细菌载体的研发以及肿瘤治疗都具有重要的意义。

Cancer is the major disease causing the death of human. Study of cancer mechanism and therapy has been the hotspot for many years. Recently, cancer bacterial therapy is becoming a novel anti-cancer method attracting researchers' interest. The results indicated bacteria could specifically target the microenvironment of solid tumor, but the mechanism is still unclear. In our previous study, we constructed an attenuated Salmonella typhimurium tumor targeting strain YB1, and developed breast and liver cancer animal model. Furthermore, we started the construction of live imaging system for observing the process of bacteria targeting tumor. In this project, we want to accomplish：1. Developing multiply fluorescence proteins, which is compatible, stable, and strong tissue penetrating, to label bacteria and cancer cells. 2. Oberering and recording the whole process of bacteria targeting tumor in whole-body, tissue, and cell levels.3. Studying the interaction between bacteria and cancer cells, bacteria and immune cells, cancer cells and immune cells in this process. Based on the studies, we try to understand the underlying mechanism in bacteria targeting tumor, to further support the study of cancer and development of bacterial vector in cancer therapy.