Zhang Hengrui, Li Dewei, Ren Huifang, Ma Zhenrui, Meng Shuqin, Qiao Yujie, Yang Jiabao, Wang Yao, Zhou Qingjun, Xie Lixin
Eye Institute of Shandong First Medical University, State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, School of Ophthalmology, Shandong First Medical University, Qingdao, 266071, P. R. China.
Adv Mater. 2025 Feb;37(8):e2408221. doi: 10.1002/adma.202408221. Epub 2025 Jan 13.
Multidrug-resistant (MDR) bacteria and their associated biofilms are major causative factors in eye infections, often resulting in blindness and presenting considerable global health challenges. Presently, mechano-bactericidal systems, which combine distinct topological geometries with mechanical forces to physically induce bacterial apoptosis, show promising potential. However, the physical interaction process between current mechano-bactericidal systems and bacteria is generally based on passive diffusion or Brownian motion and lacks the force required for biofilm penetration; thus, featuring low antibacterial efficacy. Here, a biomimetic mechano-bactericidal nanomotor (VMSNT) is synthesized by functionalizing COOH-PEG-phenylboronic acid (PBA) on virus-like mesoporous silica, with subsequent partial coating of Au caps. Enhanced by self-thermophoresis capabilities and virus-like topological shapes, VMSNT significantly improves mechanical antibacterial effects and biofilm penetration. In addition, scanning electron microscope (SEM) and confocal laser scanning microscope (CLSM) analyses demonstrate that VMSNT can precisely target bacteria within the infection microenvironment, facilitated by PBA's ability to recognize and bind to the peptidoglycan on bacterial surfaces. Remarkably, VMSNT is also effective in eliminating MDR bacteria and reducing inflammation in mice models of methicillin-resistant Staphylococcus aureus (MRSA)-infected keratitis and endophthalmitis, with minimal adverse effects. Overall, such a nanomotor presents a promising approach for addressing the challenges of ocular MDR bacterial infections.
多重耐药（MDR）细菌及其相关生物膜是眼部感染的主要致病因素，常常导致失明，并带来巨大的全球健康挑战。目前，机械杀菌系统将独特的拓扑几何结构与机械力相结合，以物理方式诱导细菌凋亡，显示出有前景的潜力。然而，当前的机械杀菌系统与细菌之间的物理相互作用过程通常基于被动扩散或布朗运动，缺乏穿透生物膜所需的力；因此，抗菌效果较低。在此，通过在病毒样介孔二氧化硅上功能化COOH-PEG-苯硼酸（PBA），随后部分包覆金帽，合成了一种仿生机械杀菌纳米马达（VMSNT）。VMSNT通过自热泳能力和病毒样拓扑形状得到增强，显著提高了机械抗菌效果和生物膜穿透能力。此外，扫描电子显微镜（SEM）和共聚焦激光扫描显微镜（CLSM）分析表明，由于PBA能够识别并结合细菌表面的肽聚糖，VMSNT可以在感染微环境中精确靶向细菌。值得注意的是，在耐甲氧西林金黄色葡萄球菌（MRSA）感染的角膜炎和眼内炎小鼠模型中，VMSNT在消除MDR细菌和减轻炎症方面也有效，且副作用最小。总体而言，这种纳米马达为应对眼部MDR细菌感染的挑战提供了一种有前景的方法。
