中文摘要：

目前临床上使用的大多数抗生素杀菌或抑菌的主要机制为：选择性的作用于细菌细胞核酸和蛋白合成系统的特定环节，妨碍细菌生命活动，导致细菌死亡．然而，细菌形态结构完整性仍然保持，导致细菌产生耐药性．最近研究发现大肠杆菌和金黄色葡萄球菌感染是一些慢性疾病发生的重要因素．纳米颗粒能够选择性的作用于徽生物表面，破坏细菌结构完整性，抑制细菌耐药性的产生．本文设计并合成一种生物相容性好且生物可降解ε-多聚桢氨酸修饰阳离子聚合物（EPL-PCL）．该多聚物能够自主装形成单分散的纳米颗粒，且对大肠杆菌、金黄色葡萄球菌和枯草芽孢杆菌具有广谱的抗菌活性．相比于ε-多聚赖氧酸，EPL—PCL纳米颗粒具有更强的抗菌活性．进一步研究发现，EPL—PCL纳米颗粒抗菌作用的主要机制为：（1）带正电的EPL-PCL纳米颗粒与带负电的细菌表面相互作用并穿透细胞壁和细胞膜，破坏细菌表面完整性，抑制细菌耐药性的生成；（2）EPL-PCL纳米颗粒暴露显著提高细菌ROS水平；（3）ROS水平升高显著的破坏细菌细胞代谢，例如提高碱性磷酸酶活性破坏细菌磷的稳态平衡．因此，本文合成的可降解ε-多聚赖氨酸修饰阳离子纳米聚合物可以作为一种有效且广谱的抗菌剂，持别是用于病原菌感染的疾病．

英文摘要：

Biocompatible and biodegradable ε-poly-L- lysine （EPL）/poly （ε-caprolactone） （PCL） copolymer was designed and synthesized. The amphiphilic EPL-PCL copolymer could easily self-assembled into monodispersed nanoparticles （NPs）, which showed a broad-spectrum antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus subtilis. Interestingly, the antibacterial efficacy of the novel NPs is more potent than the cationic peptide EPL. To explore the underlying mechanism of the biodegradable cationic NPs, various possible antibacterial pathways have been validated. The NPs have been found that they can disrupt bacterial walls/ membranes and induce the increasing in reactive oxygen species and alkaline phosphatase levels. More importantly, the self-assembled NPs induced the changes in bacterial osmotic pressure, resulting in cell invagination to form holes and cause the leakage of cytoplasm. Taken together, our results suggest that the EPL-PCL NPs can be further developed to be a promising antimicrobial agent to treat infectious diseases as surfactants and emulsifiers to enhance drug encapsulation efficiency and antimicrobial activity.