文章目录

用于近红外光诱导表达癌症治疗的工程细菌

原文发布日期：2025-03-17

英文摘要：

摘要翻译：

原文链接：

文章：

用于近红外光诱导表达癌症治疗的工程细菌

Engineered bacteria for near-infrared light-inducible expression of cancer therapeutics

原文发布日期：2025-03-17

英文摘要：

Bacteria-based therapies hold great promise for cancer treatment due to their selective tumor colonization and proliferation. However, clinical application is hindered by the need for safe, precise control systems to regulate local therapeutic payload expression and release. Here we developed a near-infrared (NIR) light-mediated PadC-based photoswitch (NETMAP) system based on a chimeric phytochrome-activated diguanylyl cyclase (PadC) and a cyclic diguanylate monophosphate-dependent transcriptional activator (MrkH). The NETMAP-engineered bacteria exhibited antitumor performance in mouse tumor models with different levels of immunogenicity. Specifically, in immunogenic lymphoma tumors, NIR-induced PD-L1 and CTLA-4 nanobodies enhanced the activation of adaptive immunity. In low-immunogenic tumors—including mouse-derived colon cancer models, an orthotopic human breast cancer cell line-derived xenograft model and a colorectal cancer patient-derived xenograft model—NIR-induced azurin and cytolysin A predominantly led to tumor inhibition. Our study identifies an NIR light-mediated therapeutic platform for engineered bacteria-based therapies with customizable outputs and precise dosage control.

摘要翻译：

细菌基底的治疗手段在癌症治疗方面具有巨大潜力，因其能够在肿瘤中精确选择性和增殖。然而，临床应用受限于需要安全、精确的控制系统来调节局部治疗性载体物质的表达和释放。在这里我们开发了一个基于近红外线（NIR）的光驱动物 PadC 基因组的光开关（NETMAP）系统，该系统基于混合光合素激活的二价酰胺合成酶（PadC）和循环二磷酸腺苷依赖性转录激活因子（MrkH）。经 NETMAP 改造的细菌在小鼠肿瘤模型（具有不同免疫性水平）中表现出抗肿瘤效果。具体来说，在免疫性淋巴瘤肿瘤中，NIR诱导的 PD-L1 和 CTLA-4 纳米体增强了适应性免疫的激活。在低免疫性肿瘤（包括小鼠导出结直肠癌模型、-xl模式的人乳腺癌细胞系去核移植模型和色素瘤患者去核移植模型）中，近红外光诱导的尿嘧啶和胞嘧啶 A 主要导致肿瘤抑制。我们的研究识别出一个基于近红外线的治疗平台，可用于工程细菌疗法，具有可定制化输出和精确的剂量控制能力。