Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371, Singapore.
Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biomaterials. 2021 May;272:120809. doi: 10.1016/j.biomaterials.2021.120809. Epub 2021 Apr 5.
Live attenuated bacteria have been used as target vehicles for genetic therapy of malignant carcinoma because they can be reprogrammed by following simple genetic rules and have the ability to target tumor hypoxic region. In this research, noninvasive Escherichia coli (E. Coli) is genetically modified through the plasmid transfection to afford E. Coli(p) with overexpressed human catalase for catalyzing HO into O in the tumor site. The produced O is consequently converted to cytotoxic O under near-infrared (NIR) light irradiation for photodynamic therapy. Chlorin e6 (Ce6) is chosen as the photosensitizer for its excellent photodynamic ability, and polydopamine (pDA) is employed to encapsulate Ce6 for its good biosafety, photothermal ability, and adhesion capacity with bacteria. Dopamine polymerizes in the presence of Ce6 to form pDA/Ce6, and then E. Coli(p) is coated with pDA/Ce6 to afford the final E. Coli(p)/pDA/Ce6. The obtained system is intravenously administrated for selective accumulation and replication in the hypoxic tumor. NIR light irradiation is introduced to enable photothermal and O-enhanced photodynamic therapy. On account of complementary combination, the system exhibits efficient antitumor effect in vitro and in vivo. Thus, the integration of genetically modified bacteria with pDA/Ce6 presents a promising application potential for precise tumor inhibition.
减毒活细菌因其可遵循简单的遗传规则重新编程且具有靶向肿瘤乏氧区域的能力，已被用作恶性癌基因治疗的靶向载体。在本研究中，通过质粒转染对非侵入性大肠杆菌（E. coli）进行基因修饰，赋予 E. coli(p) 过表达的人过氧化氢酶，以在肿瘤部位将 HO 催化为 O。所产生的 O 在近红外（NIR）光照射下进一步转化为细胞毒性 O，用于光动力治疗。选择叶绿素 e6（Ce6）作为光敏剂，因其具有优异的光动力能力，而聚多巴胺（pDA）则因其良好的生物安全性、光热能力以及与细菌的黏附能力而被用于包裹 Ce6。多巴胺在 Ce6 的存在下聚合形成 pDA/Ce6，然后用 pDA/Ce6 包裹 E. coli(p)，得到最终的 E. coli(p)/pDA/Ce6。所得到的系统通过静脉注射用于在缺氧肿瘤中选择性积累和复制。引入近红外光照射以实现光热和 O 增强的光动力治疗。由于互补组合，该系统在体外和体内均表现出高效的抗肿瘤效果。因此，将基因修饰细菌与 pDA/Ce6 结合在一起，为精确肿瘤抑制提供了有前景的应用潜力。
