传统的化疗方式在恶性肿瘤治疗中，在有效杀灭肿瘤细胞的同时，对正常组织和细胞也造成了巨大的损伤，同时对复发性肿瘤的有效率显著降低，因而肿瘤靶向治疗成为抗肿瘤研究领域的重要研究方向之一。前期研究发现某些无病原性的细菌对低氧的肿瘤组织具有靶向定殖能力，本项目将抗肿瘤药物与细菌的肿瘤靶向定殖特性结合起来开发具有靶向治疗作用的化疗方法。该课题选择目前具有非常强抗肿瘤活性的肽类抗生素polytheonamides，人工合成polytheonamides的生物合成基因簇，在常规宿主细胞中表达验证其基因簇功能的完整性；然后构建并优化全基因簇表达质粒，在具有肿瘤靶向定殖能力的细菌中进行药物的有效表达；最终将带有抗肿瘤药物合成基因簇的细菌注射入小鼠体内，进行动物体内的抗肿瘤活性检测。本研究将药物的抗肿瘤活性与细菌的肿瘤靶向定殖特性有效结合，为肿瘤的靶向治疗提供了一种新思路。

Chemotherapy in cancer has been effective in the treatment of malignant cancer, however, it has strong adverse effects and the cure rate of the recurrence is very low. These troublesome situations have spurred the emergence of tumor-targeting systems recently. Some non-pathogenic bacteria have been proved to specifically target the tumor and grow in its hypoxic microenvironment. This project is aimed at exploring the targeting therapy of cancer with bacteria as a new tumor-targeting carrier to deliver and express antineoplastics. Firstly, the biosynthetic gene cluster of the potent anti-cancer peptides, polytheonamides, will be synthesized and then were heterologous expressed in regular heterologous hosts; secondly, the expression plasmids containing the whole gene cluster will be constructed and expressed in the bacteria with the high tumor-targeting ability; lastly, the engineering bacteria will be injected into mice intravenously (i.v.) and the in vivo anti-cancer activity will be assessed. This research will provide a new strategy for curing cancer by combining the tumor-targeting bacteria and the potent antineoplastics.