里芬素加载的多电解质复合物通过醇介导的细胞吸收和氧化应激增强消除细胞内细菌
Zhaoxin Xia1, Yulong Liao2, Ge Gao1
1College of Chemistry, Sichuan University, Chengdu 610064, China.
ACS applied bio materials
|March 20, 2024
概括
这项研究开发了一种新型的多电解质复合物 (PECs@Rif),用于直接向细胞输送抗生素,通过增强药物积累和产生活性氧物种,显著改善了细胞内细菌感染的治疗.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术 纳米技术
- 传染性疾病 传染性疾病
背景情况:
- 细胞内细菌由于在细胞质中抗生素积累不良,造成了治疗挑战.
- 需要有效的策略来增强抗生素的输送和抗细胞内病原体的疗效.
研究的目的:
- 开发一种多电解质复合物 (PECs@Rif) 用于直接细胞溶液输送利芬素 (Rif) 以对抗细胞内细菌感染.
- 通过 thiol-mediated 吸收和 ROS 生产来研究增强细菌根除的机制.
主要方法:
- 使用聚-酸 (pLA) 和寡糖化物 (COS) 形成多电解质复合物 (PECs@Rif),以封装Rif.
- 与自由Rif相比,细胞吸收和细胞内药物度的评估.
- 在体外和体内使用带有细菌病的小鼠模型进行细菌根除的评估.
主要成果:
- 与自由Rif相比,PECs@Rif在细胞质中获得了3.9倍高的Rif积累.
- 该复合物促进了Rif释放,并通过芬顿反应产生了活性氧物种 (ROS),增强了细菌杀死.
- 在体外,PECs@Rif使细胞内细菌减少了2.8个数量级,显著超过了自由Rif (0.7个数量级).
- 在体内研究显示,治疗小鼠的肝脏,脏和脏中的细菌负荷大幅减少.
结论:
- 通过PECs@Rif,通过醇吸收调解Rif的直接细胞溶液输送,为治疗细胞内细菌感染提供了一个有前途的策略.
- 增强药物递送和ROS诱导的氧化应激的联合作用显著提高了抗菌功效.
- 这种方法为开发针对具有挑战性的细胞内病原体的先进疗法提供了一个可行的平台.
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