Modular-designed engineered bacteria for precision tumor immunotherapy via spatiotemporal manipulation by magnetic field

Xiaotu Ma, Xiaolong Liang, Yao Li, Qingqing Feng, Keman Cheng, Nana Ma, Fei Zhu, Xinjing Guo, Yale Yue, Guangna Liu, Tianjiao Zhang, Jie Liang, Lei Ren, Xiao Zhao () and Guangjun Nie ()
Additional contact information
Xiaotu Ma: National Center for Nanoscience and Technology
Xiaolong Liang: Peking University Third Hospital
Yao Li: National Center for Nanoscience and Technology
Qingqing Feng: National Center for Nanoscience and Technology
Keman Cheng: National Center for Nanoscience and Technology
Nana Ma: National Center for Nanoscience and Technology
Fei Zhu: National Center for Nanoscience and Technology
Xinjing Guo: National Center for Nanoscience and Technology
Yale Yue: National Center for Nanoscience and Technology
Guangna Liu: National Center for Nanoscience and Technology
Tianjiao Zhang: National Center for Nanoscience and Technology
Jie Liang: National Center for Nanoscience and Technology
Lei Ren: Research Center of Biomedical Engineering of Xiamen, Department of Biomaterials, College of Materials, Xiamen University
Xiao Zhao: National Center for Nanoscience and Technology
Guangjun Nie: National Center for Nanoscience and Technology

Nature Communications, 2023, vol. 14, issue 1, 1-22

Abstract: Abstract Micro-nano biorobots based on bacteria have demonstrated great potential for tumor diagnosis and treatment. The bacterial gene expression and drug release should be spatiotemporally controlled to avoid drug release in healthy tissues and undesired toxicity. Herein, we describe an alternating magnetic field-manipulated tumor-homing bacteria developed by genetically modifying engineered Escherichia coli with Fe3O4@lipid nanocomposites. After accumulating in orthotopic colon tumors in female mice, the paramagnetic Fe3O4 nanoparticles enable the engineered bacteria to receive and convert magnetic signals into heat, thereby initiating expression of lysis proteins under the control of a heat-sensitive promoter. The engineered bacteria then lyse, releasing its anti-CD47 nanobody cargo, that is pre-expressed and within the bacteria. The robust immunogenicity of bacterial lysate cooperates with anti-CD47 nanobody to activate both innate and adaptive immune responses, generating robust antitumor effects against not only orthotopic colon tumors but also distal tumors in female mice. The magnetically engineered bacteria also enable the constant magnetic field-controlled motion for enhanced tumor targeting and increased therapeutic efficacy. Thus, the gene expression and drug release behavior of tumor-homing bacteria can be spatiotemporally manipulated in vivo by a magnetic field, achieving tumor-specific CD47 blockage and precision tumor immunotherapy.

Date: 2023
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DOI: 10.1038/s41467-023-37225-1

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