离子基链长度和离子液体的纳米聚合物形式主导生物相容性和毒性
Yuyuan Xing1,2,3, Yanhui Hu1,2,4,5, Xiao Zhang1,2
1Beijing Key Laboratory of Solid State Battery and Energy Storage Process, State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P. R. China.
Nature communications
|July 28, 2025
概括
离子液体 (ILs) 在医学上表现有前途,但安全性是关键. 短链ILs (scILs) 比长链ILs (lcILs) 更安全,提供潜在的药物输送应用.
科学领域:
- 材料科学 材料科学 材料科学
- 纳米技术纳米技术
- 生物医学工程 生物医学工程
背景情况:
- 离子液体 (ILs) 具有多种应用,但它们的生物医学潜力受到系统生物安全数据的缺乏限制.
- 了解IL的生物相容性和毒性谱对于推进其临床使用至关重要.
研究的目的:
- 建立一个离子液体库,阐明IL结构与生物安全之间的关系.
- 研究IL纳米聚合物在生物系统中的体外和体内行为和机制.
- 评估安全ILs作为药物输送载体的潜力.
主要方法:
- 开发一个离子液体库,具有不同长度的阴性基链.
- 使用多个细胞系,细胞球体和患者衍生器官的体外研究来评估细胞毒性和细胞吸收.
- 在小鼠和狗模型中的体内评估,包括不同的给药途径 (口服,肌内,静脉注射).
- 计算分析与实验数据集成,以了解IL纳米聚合物的行为和机制.
主要成果:
- 随着阴阳基链长度的增加,ILs的生物相容性下降,短链ILs (scILs) 的毒性明显低于长链ILs (lcILs).
- 在水性环境中,ILs形成纳米聚合物; scILs被内细胞化成囊泡,而lcILs在线粒体中积聚,诱导线粒细胞衰变和亡.
- 在体内研究证实lcILs诱导线粒和亡,scILs在各种给药途径中表现出比lcIL更高的30-80倍耐受性.
- scIL纳米聚合物证明了作为不溶性药物的载体的可行性,与商业配方相比,提高了生物可用性.
结论:
- 离子液体的安全性与基链长度有很强的相关性,scILs在生物医学应用中具有有利的安全性.
- 诱导IL的细胞毒性的机制涉及线粒体积累和随后的线粒体/细胞亡.
- scILs是药物输送系统的有希望的候选者,比lcILs提供更好的生物可用性和更高的安全性.
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