Zhang Peng, Han Jinxiu, Kong Xue, Liu Shaojun, Chen Yuqing, Li Juan, Zhang Yuanqing, Wang Chuanxin, Du Lutao
Department of Clinical Laboratory, Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Shandong Engineering & Technology Research Center for Tumor Marker Detection the Second Hospital of Shandong University, Jinan 250033, China.
Department of Clinical Laboratory, Children's Hospital Affiliated to Shandong University, Jinan 250022, China.
ACS Nano. 2025 Apr 8;19(13):13202-13219. doi: 10.1021/acsnano.4c18948. Epub 2025 Mar 25.
Bacterial infections, especially drug-resistant bacterial infections, are causing increasing harm in clinical practice, and there is an urgent need to develop effective antimicrobial materials. Biomimetic DNA nanomachines have attracted much attention due to their flexible design, precise control, and high biocompatibility, but their use for bacterial inhibition has not been reported. Neutrophil extracellular traps (NETs), a network structure released by neutrophils with good bactericidal function, can be used as a superior biomimetic object for the construction of functional bacterial inhibition materials. In this study, -shaped DNA was polymerized using magnesium ions to develop reticulated DNA structures, which were used as templates to synthesize copper nanoclusters, leading to the construction of compositionally well-defined and simple reticulated DNA nanomachines. The nanomachine had a three-dimensional, reticular structure similar to that of NETs and especially had excellent antibacterial activity. More importantly, the NETs-imitated nanomachine had a multimodal bacterial inhibition mechanism. The nanomachine could target and localize around the bacteria and eliminate the biofilm, and then the DNA network structure effectively trapped and aggregated the bacteria and caused damage to the bacterial morphology and membrane structure; at the same time, the reticulated DNA nanomachine could also damage the bacterial membrane, causing the degradation and leakage of the proteins and the cellular contents and breakage of the DNA structure, ultimately causing irreversible inhibition of the bacteria. Importantly, the developed nanomachines with high biocompatibility could be used as antimicrobial biomaterials for the efficient treatment and healing of skin wounds infected with bacteria. This study develops a biomimetic DNA nanomachine that can be an excellent antibacterial biomaterial, which expands the application of DNA nanomachine in bacteriostatic and therapeutic fields; it is also an improved biomimetic NETs biomaterial, which brings distinctive design sources for biomimetic materials.
细菌感染,尤其是耐药细菌感染,在临床实践中造成的危害日益增加,因此迫切需要开发有效的抗菌材料。仿生DNA纳米机器因其灵活的设计、精确的控制和高生物相容性而备受关注,但其用于细菌抑制的研究尚未见报道。中性粒细胞胞外陷阱(NETs)是中性粒细胞释放的具有良好杀菌功能的网络结构,可作为构建功能性细菌抑制材料的优质仿生对象。在本研究中,利用镁离子聚合“-”形DNA以形成网状DNA结构,将其用作模板合成铜纳米簇,从而构建出组成明确且简单的网状DNA纳米机器。该纳米机器具有类似于NETs的三维网状结构,尤其具有出色的抗菌活性。更重要的是,模仿NETs的纳米机器具有多模式细菌抑制机制。该纳米机器能够靶向并定位在细菌周围并消除生物膜,然后DNA网络结构有效地捕获并聚集细菌,对细菌形态和膜结构造成破坏;同时,网状DNA纳米机器还能破坏细菌膜,导致蛋白质和细胞内容物降解和泄漏以及DNA结构断裂,最终对细菌产生不可逆的抑制作用。重要的是,所开发的具有高生物相容性的纳米机器可作为抗菌生物材料用于高效治疗和愈合细菌感染的皮肤伤口。本研究开发了一种可成为优异抗菌生物材料的仿生DNA纳米机器,这拓展了DNA纳米机器在抑菌和治疗领域的应用;它也是一种改良的仿生NETs生物材料,为仿生材料带来了独特的设计来源。