低氧是绝大多数实体瘤最重要的特征。研究证实，益生菌Escherichia coli Nissle 1917（EcN）作为一种兼性厌氧菌，可靶向实体瘤的内部低氧区域。聚合物纳米粒子可靶向肿瘤细胞，但利用EcN靶向性，构建EcN修饰的载药纳米粒子靶向肿瘤的效果研究较少。在前期研究基础上，本项目拟构建EcN细菌修饰聚合物载药纳米粒子，并对其靶向肿瘤效果进行研究。采用化学接枝法构建EcN修饰的聚合物载药纳米粒子，分析接枝后EcN的活力、体外考察其释放行为；通过构建多细胞球体的三维肿瘤模型，初步阐明EcN修饰的纳米粒子的肿瘤靶向性；进一步构建皮下裸鼠肿瘤模型，明确其分布及肿瘤靶向性；通过构建4T1原位乳腺癌模型，研究EcN修饰的载药纳米粒子抑制肿瘤生长和转移的效果。为构建EcN介导的靶向肿瘤低氧环境的药物载体研究奠定基础。

Hypoxia is an important characteristic in the solid tumors. Probiotics bacteria Escherichia coli Nissle 1917 (EcN) have been confirmed to be capable of active targeting to the internal hypoxia area of solid tumors, and polymer nanoparticles were also confirmed to accumulated in tumors. However, there is rarely reports about the construction of polymer drug-loading nanoparticles decorated with EcN targeting to hypoxia microenvironment in the tumor. Therefore, in this proposal, we will investigate the antitumor effects of polymer nanoparticle decorated with EcN bacteria on the basis of the previous study. Firstly, the drug delivery system comprised with EcN and nanoparticles was constructed, and the viability of EcN and drug release profiles of nanoparticles decorated with EcN were analyzed. Multicellular tumor spheroids were established for validating the tumor targeting characteristics in vitro. Furthermore, 4T1 subcutaneous tumor model was established in nude mice for investigating the biodistribution and tumor targeting of the drug delivery system. Finally, 4T1 orthotopic breast tumor model was established for validating the tumor growth and metastasis inhibition effects of the polymer nanoparticles grafted with EcN to provide the theoretical basis for constructing new drug carriers which were capable of targeting to internal hypoxia microenvironment of tumors mediated by EcN.