恶性肿瘤的生长、侵袭和转移依赖于血管生成。VEGF/VEGFR-2信号通路在肿瘤血管生成过程中起关键作用。预实验发现，表面展示小鼠VEGFR-2的重组T4噬菌体(T4-VEGFR-2)可以特异性结合VEGF，提示其可能具有抑制肿瘤血管生成的作用。本研究以T4噬菌体作为生物纳米载体，利用同源重组的原理分别将不同长度的小鼠VEGFR-2胞外区基因插入到T4噬菌体基因组，使其表达在T4噬菌体的表面，制备成具有潜在抗肿瘤血管生成活性的重组噬菌体(T4-VEGFR-2)，酶联免疫吸附试验，噬菌体滴定，斑点杂交等方法检测其与VEGF的结合能力，并且筛选出结合能力最强的重组噬菌体，通过体外实验研究重组噬菌体对血管内皮细胞增殖和迁移的影响及其可能的作用机制；建立小鼠移植瘤模型和转移模型，观察其对荷瘤小鼠的生存期、肿瘤生长、转移的抑制作用。预期开发出一种新的抗肿瘤血管生成策略，为进一步临床实验提供科学依据。

Tumor growth, invasion and metastasis are angiogenesis dependent. It has shown that, VEGF/VEGFR-2 signaling pathway plays a key role in tumor angiogenesis. Our preliminary experiments show that the recombinant bacteriophage T4 displaying of mouse vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2) can specifically binds VEGF in vitro, suggesting that it may have a role in inhibiting tumor angiogenesis. In this study, a biotherapeutic method targeting VEGFR-2 will be developed by using bacteriophage T4 as the carrier. To generate recombinant phage (T4-VEGFR-2) nanoparticles, the DNA encoding the extracellular domain of VEGFR-2 will be inserted into the genome of bacteriophage T4 by homologous recombination and VEGFR-2 protein will be displayed on the T4 phage surface. Enzyme linked immunosorbent assay (ELISA), phage titration and dot hybridization methods were used to detect their ability in combination with VEGF, and to filter out the clone with strongest affinity to VEGF. Endothelial cell proliferation and migration assays will be used to detect the potential anti-tumor angiogenic activity of the recombinant phage in vitro. Tumor xenograft model and tumor metastasis model will be established and animal survival, tumor growth and metastases will be measured to evaluate the role of anti-angiogenesis of recombinant phage in vivo. In general, the aim of this study is to establish a novel anti-angiogenic strategy by using T4 phage display systerm, and to provide scientific evidence for further clinical trials of the recombinant phage (T4-VEGFR-2) nanoparticles.