Hu Tingting, Chu Dandan, Cui Haohao, Wang Shibo, Wang Mengke, Liang Ruizheng, Li Jingguo, Li Zhanrong
Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, PR China.
State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, PR China.
Mater Today Bio. 2025 Jun 16;33:101998. doi: 10.1016/j.mtbio.2025.101998. eCollection 2025 Aug.
Bacterial keratitis caused by microbial invasion represents a significant cause of visual impairment characterized by corneal perforation, epithelial defect, intense pain, and conjunctival congestion. The widespread misuse of antibiotic eye drops in clinical treatment has accelerated the global rise of antibiotic-resistant infections, dimming the prospects for antibiotic therapy. In response, inorganic nanomaterial-based antibacterial eye drops have been developed for bacterial keratitis leveraging their structural controllability, composition diversity and ease of functionalization, However, they typically exert antibacterial effects with the assistance of laser, ultrasound, or X-ray irradiation that may cause irritation or damage to the human eye, or involve intricate structural modifications for antibacterial activation. Herein, we propose zwitterionic chitosan-modified defective amorphous ZnCuAl-layered double hydroxide nanosheets (ZC@a-LDH) as an antibacterial agent for bacterial keratitis treatment. ZC@a-LDH nanosheets demonstrate significantly enhanced antimicrobial efficacy compared with their defect-free counterparts, effectively suppressing bacterial proliferation at a minimum inhibitory concentration of 12 μg mL without relying on external stimuli. The enhanced antimicrobial performance may be attributed to the combined action of electrostatic interactions, antibacterial ions (Zn/Cu) and enhanced charge transport facilitated by structural defects. Notably, ZC@a-LDH antibacterial eye drops demonstrate effective intervention in bacterial keratitis in mice, outperforming the conventional tobramycin in therapeutic efficacy.
由微生物入侵引起的细菌性角膜炎是导致视力损害的一个重要原因，其特征为角膜穿孔、上皮缺损、剧痛和结膜充血。临床治疗中抗生素眼药水的广泛滥用加速了全球抗生素耐药性感染的增加，使抗生素治疗的前景变得黯淡。作为应对措施，基于无机纳米材料的抗菌眼药水已被开发用于治疗细菌性角膜炎，利用其结构可控性、成分多样性和易于功能化的特点。然而，它们通常需要在激光、超声或X射线照射的辅助下发挥抗菌作用，这可能会对人眼造成刺激或损伤，或者涉及复杂的结构修饰以激活抗菌性能。在此，我们提出两性离子壳聚糖修饰的缺陷型非晶态ZnCuAl层状双氢氧化物纳米片（ZC@a-LDH）作为治疗细菌性角膜炎的抗菌剂。与无缺陷的同类纳米片相比，ZC@a-LDH纳米片表现出显著增强的抗菌效果，在最低抑菌浓度为12μg/mL时能有效抑制细菌增殖，且不依赖外部刺激。抗菌性能的增强可能归因于静电相互作用、抗菌离子（锌/铜）以及结构缺陷促进的电荷传输的共同作用。值得注意的是，ZC@a-LDH抗菌眼药水在小鼠细菌性角膜炎中显示出有效的干预作用，治疗效果优于传统的妥布霉素。
