目的：细菌介导的肿瘤治疗在癌症治疗方面显示出巨大的潜力。然而，可在肿瘤中表达和释放治疗蛋白的细菌单一疗法的疗效被发现并不令人满意。迄今为止，与细菌单一疗法相比，协同疗法已成为一种有前途的方法，可以实现更强的治疗效果。在体内可视化这些肿瘤归巢细菌并引导它们表达和释放原位治疗蛋白是一个挑战。过程：我们开发了一种工程细菌（命名为CGB@ICG），该细菌在基因上整合了声报告蛋白和热诱导ClyA表达基因电路，并在细菌表面用吲哚菁绿进行化学修饰。声报告蛋白和吲哚菁绿的存在有利于通过超声造影和光学成像实现CGB@ICG的可视化，从而可以引导声波或激光精确照射这些细菌，从而通过声学诱导ClyA蛋白的表达。 - 或光热效应。 ClyA蛋白在肿瘤中的表达和分泌，与光热疗法相结合，大大增强了工程菌的抗肿瘤功效，并提高了其生物安全性。结果：我们成功地进行了 CGB@ICG 体内多模态成像，从而远程控制了肿瘤中 ClyA 蛋白的表达。体内实验表明，细菌介导疗法联合光热疗法与其他组相比，肿瘤体积迅速缩小，而联合治疗组的肿瘤体积持续缩小，甚至实现完全愈合。因此，联合治疗不仅降低了肿瘤的生长速度，而且还可以长期阻止肿瘤细胞的增殖。结论：我们的研究表明，CGB@ICG 作为一种有效的显像剂和递送载体，将工程细菌与光热疗法相结合，为肿瘤治疗带来了巨大的希望。© 作者。

Purpose: Bacteria-mediated tumor therapy has showed promising potential for cancer therapy. However, the efficacy of bacterial monotherapy treatment which can express and release therapeutic proteins in tumors has been found to be unsatisfactory. To date, synergistic therapy has emerged as a promising approach to achieve stronger therapeutic outcomes compared to bacterial monotherapy. It is a challenge to visualize these tumor-homing bacteria in vivo and guide them to express and release in situ therapeutic proteins. Procedure: We have developed a kind of engineered bacteria (named CGB@ICG) genetically incorporating acoustic reporter proteins and thermo-inducible ClyA expression gene circuit and chemically modified with indocyanine green on the bacterial surface. The presence of acoustic reporter proteins and indocyanine green facilitates the visualization of CGB@ICG via contrast-enhanced ultrasound imaging and optical imaging, making it possible to guide the sound wave or laser to irradiate precisely these bacteria for inducing the expression of ClyA protein via acoustic- or photothermal effects. The expression and secretion of ClyA protein in the tumor, combined with photothermal therapy, greatly enhanced the anti-tumor efficacy of the engineered bacteria and improved their biosafety. Results: We successfully performed multimodal imaging of CGB@ICG in vivo resulting in remoting control the expression of ClyA protein in tumor. In vivo experiments showed that bacteria-mediated therapy combined photothermal therapy exhibited a rapid decrease in tumor volume compared to other groups, while the tumor volume of the combination therapy group continued to decrease and even achieved complete healing. Thus, combination therapy not only reduced the rate of tumor growth but also prevented the proliferation of tumor cells for an extended period. Conclusion: Our study demonstrated that CGB@ICG serves as an efficacious imaging agent and delivery vector to combine engineered bacteria with photothermal therapy, holding great promise for tumor treatment.© The author(s).