Key Laboratory of Medical Imaging Precision Theranostics and Radiation Protection, College of Hunan Province, the Affiliated Changsha Central Hospital, University of South China, 161 Shaoshan South Road, Changsha, Hunan Province (China).
Institute of Medical Imaging, Hengyang Medical School, University of South China, 28 Changsheng West Road, Hengyang, Hunan Province (China).
Theranostics. 2024 Sep 9;14(15):5945-5964. doi: 10.7150/thno.98257. eCollection 2024.
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 and guide them to express and release in situ therapeutic proteins. 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. We successfully performed multimodal imaging of CGB@ICG resulting in remoting control the expression of ClyA protein in tumor. 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. 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.
细菌介导的肿瘤治疗在癌症治疗方面显示出了很大的潜力。然而，在肿瘤中表达和释放治疗性蛋白的细菌单疗法的疗效并不令人满意。迄今为止，协同治疗已成为一种很有前途的方法，可以获得比细菌单疗法更强的治疗效果。可视化这些肿瘤归巢细菌并引导它们在原位表达和释放治疗性蛋白是一个挑战。我们开发了一种工程细菌（命名为 CGB@ICG），它在基因上整合了声敏报告蛋白和热诱导型 ClyA 表达基因回路，并在细菌表面进行了吲哚菁绿的化学修饰。声敏报告蛋白和吲哚菁绿的存在使得 CGB@ICG 可以通过对比增强超声成像和光学成像进行可视化，从而可以引导声或激光精确照射这些细菌，通过声或光热效应诱导 ClyA 蛋白的表达。肿瘤中 ClyA 蛋白的表达和分泌，结合光热治疗，极大地增强了工程细菌的抗肿瘤疗效，并提高了其生物安全性。我们成功地对 CGB@ICG 进行了多模态成像，实现了对肿瘤中 ClyA 蛋白表达的远程控制。实验表明，与其他组相比，细菌介导的治疗联合光热治疗可使肿瘤体积迅速减小，而联合治疗组的肿瘤体积继续减小，甚至完全愈合。因此，联合治疗不仅降低了肿瘤生长的速度，而且还在很长一段时间内阻止了肿瘤细胞的增殖。我们的研究表明，CGB@ICG 是一种有效的成像剂和递送载体，可以将工程细菌与光热治疗相结合，为肿瘤治疗带来了很大的希望。
