Du Fangyuan, Niu Jingqi, Hong Yu, Fang Xue, Geng Zhihui, Liu Jing, Xu Fangqi, Liu Tingshu, Chen Qifan, Zhai Jingbo, Miao Beiliang, Liu Shiwei, Zhang Yi, Chen Zeliang
Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, People's Republic of China.
College of Animal Husbandry & Veterinary Medicine, Jinzhou Medical University, Jinzhou, 121001, People's Republic of China.
Int J Nanomedicine. 2025 Jan 13;20:523-540. doi: 10.2147/IJN.S498672. eCollection 2025.
Antibiotic resistance of many bacteria, including Methicillin-resistant (MRSA), has become a major threat to global health. Zinc Oxide Quantum dots (ZnO-QDs) show good antibacterial activity, but most of them are insoluble in water, limiting their application range, and there is a lack of research on drug resistance inducement.
The water-soluble zinc oxide quantum dots modified by APTES (ZnO@APTES QDs) were prepared by a microwave assisted synthesis. Then ZnO@APTES QDs were characterized through various methods. After confirmation of synthesized ZnO@APTES QDs, its bactericidal effect on MRSA was detected through in vitro and in vivo experiments, and its mechanism of action was analyzed.
Characterization analysis revealed that the ZnO@APTES QDs have a particle size of 5 nm. The minimum inhibitory concentrations (MIC) were determined to be 64 µg mL for () and 32 µg mL for MRSA. The ZnO@APTES QDs showed significant inhibition of MRSA biofilm formation and effectively disrupted mature biofilms. Notably, the ZnO@APTES QDs did not induce tolerance or resistance even after 30 days of repeated exposure, whereas antibiotics led to a rise in bacterial MIC within 3 days and a 60-fold increase after 30 days. Mechanistic analysis indicated that the positively charged quantum dots interact with bacterial surfaces, altering membrane fluidity. Once inside the bacteria, the ZnO@APTES QDs generate reactive oxygen species (ROS), causing DNA damage and bacterial cell death. Moreover, the ZnO@APTES QDs possessed good biocompatibility and demonstrated significant therapeutic efficacy against drug-resistant bacterial infections in both macrophage and mouse wound infection models.
In summary, we have synthesized a highly effective water-soluble ZnO@APTES QDs that shows strong antibacterial and therapeutic efficacy against MRSA and other bacteria. The ZnO@APTES QDs holds significant potential for development as a new treatment agent for combating antibiotic-resistant infections.
包括耐甲氧西林金黄色葡萄球菌（MRSA）在内的许多细菌的抗生素耐药性已成为全球健康的重大威胁。氧化锌量子点（ZnO-QDs）显示出良好的抗菌活性，但大多数不溶于水，限制了其应用范围，并且缺乏关于耐药性诱导的研究。
通过微波辅助合成制备了经APTES修饰的水溶性氧化锌量子点（ZnO@APTES QDs）。然后通过各种方法对ZnO@APTES QDs进行表征。在确认合成的ZnO@APTES QDs后，通过体外和体内实验检测其对MRSA的杀菌作用，并分析其作用机制。
表征分析表明，ZnO@APTES QDs的粒径为5nm。测定其对（）的最低抑菌浓度（MIC）为64μg/mL，对MRSA为32μg/mL。ZnO@APTES QDs对MRSA生物膜形成有显著抑制作用，并能有效破坏成熟生物膜。值得注意的是，即使反复暴露30天，ZnO@APTES QDs也不会诱导耐受性或耐药性，而抗生素在3天内导致细菌MIC升高，30天后增加60倍。机制分析表明，带正电荷的量子点与细菌表面相互作用，改变膜流动性。一旦进入细菌内部，ZnO@APTES QDs产生活性氧（ROS），导致DNA损伤和细菌细胞死亡。此外，ZnO@APTES QDs具有良好的生物相容性，并在巨噬细胞和小鼠伤口感染模型中对耐药细菌感染显示出显著的治疗效果。
综上所述，我们合成了一种高效的水溶性ZnO@APTES QDs，它对MRSA和其他细菌显示出强大的抗菌和治疗效果。ZnO@APTES QDs作为一种对抗抗生素耐药性感染的新型治疗剂具有巨大的开发潜力。
