Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190, China; France-China International Laboratory of Evolution and Development of Magnetotactic Multicellular Organisms, Beijing, China.
Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190, China; France-China International Laboratory of Evolution and Development of Magnetotactic Multicellular Organisms, Beijing, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
J Control Release. 2022 Nov;351:941-953. doi: 10.1016/j.jconrel.2022.09.059. Epub 2022 Oct 11.
Since magnetic micro/nano-materials can serve as multifunctional transducers for remote control of cell functions by applying diverse magnetic fields, magnetic cell manipulation provides a highly promising tool in biomedical research encompassing neuromodulation, tissue regeneration engineering and tumor cell destruction. Magnetotactic bacteria (MTB), which contain natural magnetic materials, can sensitively respond to external magnetic fields via their endogenous magnetosome chains. Here, we developed a technique for magnetotactic bacteria-based cell modulation and tumor suppression combined with a swing magnetic field. We enabled MTB cells to recognize and bind to mammalian tumor cells via functional modification with RGD peptides onto the surfaces of MTB cells, and RGD-modified MTB bacteria could interact with the targeted tumor cells effectively. The magnetic torque, which was due to the interaction of the long magnetosome chain inside the MTB bacterial cell and the applied swing magnetic field, could result in obvious swing magnetic behaviors of the modified MTB bacteria bound to tumor cell surfaces and thus subsequently exert a sustained magnetomechanical oscillation on the tumor cell surfaces, which could induce a significant activation of Ca ion influx in vitro and tumor growth inhibition in vivo. These findings suggest that MTB cells mediated magnetomechanical stimulation, which is remotely controlled by dynamic magnetic fields, as an effective way to regulate cell signaling and treat tumor growth, which will shed the light on further biomedical applications utilizing whole magnetotactic bacteria.
由于磁性微/纳米材料可以作为多功能换能器，通过施加各种磁场来远程控制细胞功能，因此磁细胞操作提供了一种在神经调节、组织再生工程和肿瘤细胞破坏等生物医学研究中极具前景的工具。具有天然磁性材料的趋磁细菌 (MTB) 可以通过其内源磁小体链对内源性磁小体链对外界磁场做出敏感响应。在这里，我们开发了一种结合摆动磁场的基于趋磁细菌的细胞调节和肿瘤抑制技术。我们通过在 MTB 细胞表面用 RGD 肽进行功能修饰，使 MTB 细胞能够识别和结合哺乳动物肿瘤细胞，并且 RGD 修饰的 MTB 细菌可以有效地与靶向肿瘤细胞相互作用。由于 MTB 细菌细胞内长磁小体链与施加的摆动磁场之间的相互作用产生的磁转矩，导致与肿瘤细胞表面结合的修饰 MTB 细菌表现出明显的摆动磁行为，从而在肿瘤细胞表面持续施加磁机械振荡，这可以在体外显著激活 Ca2+ 离子内流，并在体内抑制肿瘤生长。这些发现表明，MTB 细胞介导的磁机械刺激可以通过动态磁场远程控制，作为调节细胞信号和治疗肿瘤生长的有效方法，这将为进一步利用完整趋磁细菌的生物医学应用提供启示。
