Zhen Jian Bin, Yi Jiajia, Ding Huan Huan, Yang Ke-Wu
Department of Materials Engineering, Taiyuan Institute of Technology, Taiyuan 030008, China.
School of Materials Science and Engineering, North University of China,Taiyuan 030051, China.
ACS Omega. 2022 Aug 17;7(34):29909-29922. doi: 10.1021/acsomega.2c02855. eCollection 2022 Aug 30.
The overuse of antibiotics exacerbates the development of antibiotic-resistant bacteria, threatening global public health, while most traditional antibiotics act on specific targets and sterilize through chemical modes. Therefore, it is a desperate need to design novel therapeutics or extraordinary strategies to overcome resistant bacteria. Herein, we report a positively charged nanocomposite PNs-Cur with a hydrodynamic diameter of 289.6 nm, which was fabricated by ring-opening polymerization of ε-caprolactone and Z-Lys--carboxyanhydrides (NCAs), and then natural curcumin was loaded onto the PCL core of PNs with a nanostructure through self-assembly, identified through UV-vis, and characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Especially, the self-assembly dynamics of PNs was simulated through molecular modeling to confirm the formation of a core-shell nanostructure. Biological assays revealed that PNs-Cur possessed broad-spectrum and efficient antibacterial activities against both Gram-positive and Gram-negative bacteria, including drug-resistant clinical bacteria and fungus, with MIC values in the range of 8-32 μg/mL. Also, in vivo evaluation showed that PNs-Cur exhibited strong antibacterial activities in infected mice. Importantly, the nanocomposite did not indeed induce the emergence of drug-resistant bacterial strains even after 21 passages, especially showing low toxicity regardless of in vivo or in vitro. The study of the antibacterial mechanism indicated that PNs-Cur could indeed destruct membrane potential, change the membrane potential, and cause the leakage of the cytoplasm. Concurrently, the released curcumin further plays a bactericidal role, eventually leading to bacterial irreversible apoptosis. This unique bacterial mode that PNs-Cur possesses may be the reason why it is not easy to make the bacteria susceptible to easily produce drug resistance. Overall, the constructed PNs-Cur is a promising antibacterial material, which provides a novel strategy to develop efficient antibacterial materials and combat increasingly prevalent bacterial infections.
抗生素的过度使用加剧了耐药菌的产生，威胁着全球公共卫生，而大多数传统抗生素作用于特定靶点并通过化学方式杀菌。因此，迫切需要设计新的治疗方法或特殊策略来对抗耐药菌。在此，我们报道了一种水动力直径为289.6 nm的带正电荷的纳米复合材料PNs-Cur，它是通过ε-己内酯与Z-赖氨酸-N-羧酸酐（NCAs）的开环聚合反应制备而成，然后通过自组装将天然姜黄素负载到具有纳米结构的PNs的聚己内酯核上，通过紫外可见光谱进行鉴定，并通过扫描电子显微镜（SEM）和动态光散射（DLS）进行表征。特别地，通过分子模拟对PNs的自组装动力学进行了模拟，以确认核壳纳米结构的形成。生物学实验表明，PNs-Cur对革兰氏阳性菌和革兰氏阴性菌均具有广谱高效的抗菌活性，包括耐药临床菌株和真菌，其最低抑菌浓度（MIC）值在8-32 μg/mL范围内。此外，体内评估表明PNs-Cur在感染小鼠中表现出强大的抗菌活性。重要的是，即使经过21代传代，该纳米复合材料也并未诱导耐药菌株的出现，尤其在体内和体外均显示出低毒性。抗菌机制研究表明，PNs-Cur确实可以破坏膜电位，改变膜电位，并导致细胞质泄漏。同时，释放的姜黄素进一步发挥杀菌作用，最终导致细菌不可逆凋亡。PNs-Cur所具有的这种独特的杀菌模式可能是其不易使细菌产生耐药性的原因。总体而言，构建的PNs-Cur是一种有前景的抗菌材料，为开发高效抗菌材料和对抗日益普遍的细菌感染提供了一种新策略。
