Wang Bo, Qin Youwan, Liu Jie, Zhang Zefei, Li Wenhao, Pu Guangjin, Yuanhe Zhuoran, Gui Xin, Chu Maoquan
Research Center for Translational Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, P. R. China.
Institute of Biophysics, Chinese Academy of Science, Beijing 100101, P. R. China.
ACS Appl Mater Interfaces. 2023 Jan 18;15(2):2747-2759. doi: 10.1021/acsami.2c19960. Epub 2023 Jan 6.
Bacteria-mediated cancer therapy has attracted much attention in recent years. However, using magnetotactic bacteria as both a drug carrier and a drug for cancer therapy has never been reported. Herein, we incorporated a photosensitizer chlorin e6 (Ce6) into the strain AMB-1 through a chemical bond or physical blending. A chemical reaction was finally selected for fabricating AMB-1/Ce6 micromotors, as such micromotors exhibited high drug payload and normal bacterial activities. An interesting finding is that AMB-1 is not only an excellent drug carrier but also a unique drug that could inhibit mouse tumor growth. We also, for the first time, demonstrated that AMB-1 is a photosensitizer. Under laser irradiation, micromotors killed cancer cells with high efficiency due to the high-level reactive oxygen species generated by the micromotors. Micromotors could target the hypoxic and normoxic regions in vitro via both the active swimming of AMB-1 and external magnetic field guidance. Micromotors showed high tumor-homing ability owing to the above double targeting mechanisms. After injection with the micromotors followed by magnetic field guidance and laser irradiation, the growth of mouse tumors was significantly inhibited owing to the AMB-1-based biotherapy and phototoxicity of AMB-1 and Ce6. This micromotor-mediated tumor-targeted therapy strategy may be a great platform for treating many types of solid tumors.
近年来，细菌介导的癌症治疗备受关注。然而，将趋磁细菌用作药物载体和癌症治疗药物的情况尚未见报道。在此，我们通过化学键合或物理混合将光敏剂二氢卟吩e6（Ce6）掺入AMB-1菌株中。最终选择化学反应来制备AMB-1/Ce6微马达，因为这种微马达具有高载药量和正常的细菌活性。一个有趣的发现是，AMB-1不仅是一种出色的药物载体，还是一种能够抑制小鼠肿瘤生长的独特药物。我们还首次证明AMB-1是一种光敏剂。在激光照射下，微马达由于产生高水平的活性氧而高效杀死癌细胞。微马达可以通过AMB-1的主动游动和外部磁场引导在体外靶向缺氧和正常氧区域。由于上述双重靶向机制，微马达显示出高肿瘤归巢能力。注射微马达后，在磁场引导和激光照射下，由于基于AMB-1的生物疗法以及AMB-1和Ce6的光毒性，小鼠肿瘤的生长受到显著抑制。这种微马达介导的肿瘤靶向治疗策略可能是治疗多种实体瘤的一个很好的平台。
