Institute of Biomedical Engineering, College of Life Science, Qingdao University, Qingdao 266071, PR China.
Department of Urology Key Laboratory of Urinary System Diseases, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China.
J Colloid Interface Sci. 2023 Sep;645:933-942. doi: 10.1016/j.jcis.2023.04.149. Epub 2023 May 3.
Antibacterial nanomaterials provide promising alternative strategies to combat the bacterial infection due to deteriorating resistance. However, few have been practically applied due to the lack of clear antibacterial mechanisms. In this work, we selected good-biocompatibility iron-doped CDs (Fe-CDs) with antibacterial activity as a comprehensive research model to systematically reveal the intrinsic antibacterial mechanism. Through energy dispersive spectroscopy (EDS) mapping of in situ ultrathin sections of bacteria, we found that a large amount of iron was accumulated inside the bacteria treated with Fe-CDs. Then, combining the data of cell level and transcriptomics, it can be elucidated that Fe-CDs could interact with cell membranes, enter bacterial cells through iron transport and infiltration, increase intracellular iron levels, trigger increased reactive oxygen species (ROS), and lead to disruption of Glutathione (GSH)-dependent antioxidant mechanisms. Excessive ROS further leads to lipid peroxidation and DNA damage in cells, lipid peroxidation destroys the integrity of the cell membrane, and finally leads to the leakage of intracellular substances resulting in bacterial growth inhibition and death. This result provides important insights into the antibacterial mechanism of Fe-CDs and further provides a basis for the deep application of nanomaterials in biomedicine.
抗菌纳米材料为应对日益严重的耐药性细菌感染提供了有前途的替代策略。然而,由于缺乏明确的抗菌机制,很少有抗菌纳米材料实际应用。在这项工作中,我们选择了具有抗菌活性且生物相容性良好的铁掺杂 CDs(Fe-CDs)作为综合研究模型,系统地揭示了其内在的抗菌机制。通过对细菌原位超薄切片的能谱(EDS)图谱分析,我们发现大量铁被积累在经过 Fe-CDs 处理的细菌内部。然后,结合细胞水平和转录组学的数据,可以阐明 Fe-CDs 可以与细胞膜相互作用,通过铁转运和渗透进入细菌细胞,增加细胞内铁水平,引发活性氧(ROS)增加,导致谷胱甘肽(GSH)依赖性抗氧化机制破坏。过量的 ROS 进一步导致细胞内脂质过氧化和 DNA 损伤,脂质过氧化破坏细胞膜的完整性,最终导致细胞内物质泄漏,导致细菌生长抑制和死亡。这一结果为 Fe-CDs 的抗菌机制提供了重要的见解,并为纳米材料在生物医学中的深入应用提供了依据。