基因工程菌介导的可控微型生物机器人用于hSSTR2靶向的肿瘤核素诊疗

如何最大限度的提高肿瘤内药物传递效率是目前癌症诊断与治疗的挑战。众多药物传递系统中，开发具有临床转化前景的安全高效肿瘤靶向载体更具意义。大肠杆菌Nissle 1917（EcN）是目前临床常用的益生菌，其兼性厌氧性驱使它更倾向于到乏氧区生存繁殖，而肿瘤正好为EcN提供了良好的生存环境。因此EcN选择性地游到肿瘤区域内大量繁殖，使得瘤内细菌数量将高于正常器官数千倍，甚至显著高于注射的菌量，展现出具有优异的肿瘤靶向性和定殖性。利用这一特点，本研究将EcN开发成携带hSSTR2报告基因并可远程控制hSSTR2表达的微型生物机器人，高效输送hSSTR2到肿瘤部位，联合68Ga/177Lu-DOTA TATE可实现肿瘤的核素显像和治疗。大肠杆菌EcN和68Ga/177Lu-DOTA TATE均为临床批准用药，本项目巧妙的将它们结合起来发挥优势，为肿瘤的诊断和治疗提供新思路，将具有巨大的临床转化潜力。

How to maximize the delivery efficiency is the challenge of tumor diagnosis and therapy. Among drug delivery systems, it is more meaningful to develop safe and efficient tumor-targeting vectors with clinical transformation prospects. Escherichia coli Nissle 1917 (EcN) is a commonly used probiotic in clinical practice. Its facultative anaerobic property drives it to the hypoxic area for survival and reproduction, and tumors provide a good living environment for EcN. Therefore, EcN selectively swims into the tumor and reproduces in large numbers, so that the number of bacteria in the tumor will be thousands of times higher than normal organs or even significantly higher than the amount of bacteria injected, showing excellent tumor targeting and colonization. Utilizing this feature, this study developed EcN into a micro-bio-robot that carries the hSSTR2 reporter gene and remotely control hSSTR2 expression，efficiently transport hSSTR2 to the tumor site, and combined with 68Ga / 177Lu-DOTA TATE to realize radionuclide imaging and therapy. The EcN and 68Ga / 177Lu-DOTA TATE are all clinically approved, this project combines them to exert their advantages, which will bring new ideas to the diagnosis and therapy of tumors, showing excellent clinical transformation potential.