College of Medicine, Pingdingshan University, Pingdingshan, Henan 467000, China; College of Chemistry & Pharmacy, Shaanxi Key Laboratory of Natural Products & Chemical Biology, Northwest A&F University, Yangling, Shaanxi 712100, China.
College of Medicine, Yan'an University, Yan'an, Shaanxi 716000, China; College of Chemistry & Pharmacy, Shaanxi Key Laboratory of Natural Products & Chemical Biology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Int J Biol Macromol. 2023 Aug 1;245:125506. doi: 10.1016/j.ijbiomac.2023.125506. Epub 2023 Jun 24.
Pathogenic bacteria residing inside cells could cause disruption of cellular metabolic balance. Therefore, basing on high oxidative stress response of the intracellular bacteria infected micro-environment, a novel amphipathic micelle (HATAD-TCS) was developed consisting of hyaluronic acid-derivative and reactive oxygen species (ROS) - responsive group and antibacterial agent triclosan (TCS). ROS-generating cinnamaldehyde (CA) was incorporated into ROS-cleavable linkages which are future linked to the 1-decylamine to form hydrophobicity. The cinnamaldehyde released did not just killed bacteria however, also maintained intracellular ROS levels. In this study, the HATAD-TCS micelles have been characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS). The HATAD-TCS micelles could release drug gradually upon exposure to endogenous ROS being caused by infected intracellular bacteria. Furthermore, the more promising therapeutic effect of the HATAD-TCS micelles was observed in a mouse pneumonia model. These results might highlight a ROS-responsive hyaluronic acid-based nanoparticle, which could effectively treat intracellular bacterial infections.
驻留在细胞内的致病菌可能会破坏细胞代谢平衡。因此，基于受感染细胞内细菌的高氧化应激反应微环境，设计了一种新型两亲性胶束（HATAD-TCS），它由透明质酸衍生物和活性氧（ROS）响应基团以及抗菌剂三氯生（TCS）组成。生成 ROS 的肉桂醛（CA）被掺入 ROS 可裂解键中，这些键未来与 1-癸胺相连以形成疏水性。释放的肉桂醛不仅杀死了细菌，而且还维持了细胞内的 ROS 水平。在这项研究中，通过扫描电子显微镜（SEM）和动态光散射（DLS）对 HATAD-TCS 胶束进行了表征。HATAD-TCS 胶束在受到感染细胞内细菌引起的内源性 ROS 作用时，可以逐渐释放药物。此外，在小鼠肺炎模型中观察到 HATAD-TCS 胶束更有前途的治疗效果。这些结果可能突出了一种基于 ROS 响应的透明质酸纳米粒子，它可以有效治疗细胞内细菌感染。
