Traditional cancer therapies, such as surgery treatment, radiotherapy, and chemotherapy, often fail to completely eliminate tumor cells in an anaerobic microenvironment of tumor regions. In contrast to these traditional cancer therapies, the use of targeted delivery vectors to deliver anticancer genes or antitumor drugs to hypoxic areas in tumors is the most clinically promising cancer treatment with rapid development in recent years. In this study, E.coli Nissle 1917 (EcN), an intestinal probiotic, was utilized as a targeted transport vector to deliver p53 and Tum-5 protein to tumor hypoxic regions. The tumor-targeting characteristics of EcN were investigated using luciferase LuxCDABE operon, and the results demonstrated that EcN could specifically accumulate in the solid tumor areas of SMMC-7721 tumor-bearing BALB/c nude mice. The Tum 5-p53 bifunctional proteins were initially constructed and then delivered to solid tumor regions by using the targeted transporter EcN for cancer therapy. The antitumor effect and safety of three engineered bacteria, namely, EcN (Tum-5), EcN (p53), and EcN (Tum 5-p53), were also examined. The calculated tumor volume and tumor weight indicated that these three engineered bacteria could inhibit the growth of human hepatoma SMMC-7721 cells, and the antitumor effect of EcN (Tum 5-p53) expressing the Tum 5-p53 fusion protein was significantly better than those of EcN (Tum-5) and EcN (p53) alone. Immunofluorescence demonstrated that the expression of Ki-67, a nuclear proliferation-related protein, was inhibited in the tumor areas of the groups treated with the engineered bacteria, whereas the expression of caspase-3 was upregulated. The expression trends of Ki-67 and caspase-3 were consistent with the different antitumor efficacies of these three engineered bacteria. EcN did not elicit obvious side effects on mice. This research not only provids a foundation for tumor-targeted therapy but also contributes greatly to the development of antitumor agents and anticancer proteins.

中文翻译：

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肠道益生菌大肠杆菌Nissle 1917作为将p53和Tum-5递送至实体瘤进行癌症治疗的靶向载体。

传统的癌症疗法，例如手术治疗，放疗和化学疗法，通常无法完全消除肿瘤区域厌氧微环境中的肿瘤细胞。与这些传统的癌症疗法相反，使用靶向递送载体将抗癌基因或抗肿瘤药物递送至肿瘤中的低氧区域是近年来临床上最有希望且发展迅速的癌症疗法。在这项研究中，肠道益生菌大肠杆菌Nissle 1917（EcN）被用作靶向转运载体，将p53和Tum-5蛋白转运至肿瘤缺氧区域。使用荧光素酶LuxCDABE操纵子研究了EcN的肿瘤靶向特性，结果表明EcN可以在SMMC-7721荷瘤BALB / c裸鼠的实体瘤区域特异性积聚。最初构建了Tum 5-p53双功能蛋白，然后使用靶向转运蛋白EcN将其递送至实体肿瘤区域进行癌症治疗。还检查了三种工程菌，即EcN（Tum-5），EcN（p53）和EcN（Tum 5-p53）的抗肿瘤作用和安全性。计算出的肿瘤体积和肿瘤重量表明这三种工程菌可以抑制人肝癌SMMC-7721细胞的生长，表达Tum 5-p53融合蛋白的EcN（Tum 5-p53）的抗肿瘤作用明显优于那些。单独的EcN（Tum-5）和EcN（p53）。免疫荧光显示，核增殖相关蛋白Ki-67的表达在用工程菌处理的组的肿瘤区域受到抑制，而caspase-3的表达上调。Ki-67和caspase-3的表达趋势与这三种工程菌的不同抗肿瘤功效一致。EcN对小鼠没有引起明显的副作用。这项研究不仅为肿瘤靶向治疗奠定了基础，而且为抗肿瘤药物和抗癌蛋白的发展做出了巨大贡献。