脂质组成对脂质体与THP-1-衍生巨细胞相互作用的影响
Ryoya Ibuki1, Takashi Tokui1, Masaya Kuriyama1
1School of Pharmacy, Kitasato University.
Biological & pharmaceutical bulletin
|March 27, 2024
概括
脂质体中的胆固醇含量影响其细胞吸收效率,用于治疗肺部疾病. 通过胆固醇控制的更高的膜流动性增强了蛋白质吸附和巨细胞对DPPC/Chol脂质体的吸收.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术 纳米技术
- 药理学 药理学是指药理学的学科.
背景情况:
- 针对巨细胞的脂质体配方正在出现,用于治疗肺部疾病.
- 了解细胞吸收机制对于优化脂质体有效性至关重要,特别是在非结核性菌根性肺病中.
研究的目的:
- 为了研究脂质组成,特别是胆固醇比率对巨细胞对1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) /胆固醇 (Chol) 脂质体的细胞吸收的影响.
- 阐明细胞吸收途径,并确定影响脂质体-巨细胞相互作用的关键因素.
主要方法:
- 合成的DPPC/Chol脂质体大约200纳米大小,胆固醇分子比例不同 (80/20,60/40,67/33).
- 评估了使用1,6-二-1,3,5-三烯异构的脂质体膜流动性.
- 在使用内细胞和细胞检测的THP-1衍生巨细胞中研究了细胞吸收机制.
- 通过抗体阻断实验,分析了蛋白质对脂质体表面的吸附,并评估了特定受体 (低密度脂蛋白受体,掠食受体B1型) 的作用.
主要成果:
- 具有较高DPPC/Chol比率 (80/20 mol%) 的脂质体表现出更大的膜流动性.
- DPPC/Chol脂质体 (80/20和67/33mol%) 通过克拉特林和洞穴介导的内细胞和细胞内化.
- 在DPPC/Chol (80/20 mol%) 脂质体上观察到增强的蛋白质吸附,与细胞吸收增加相关.
- 由于对LDL受体和SR-B1的抗体,DPPC/Chol (80/20 mol%) 脂质体的摄入量显著减少,这表明它们参与了该过程.
结论:
- 脂质体膜流动性由胆固醇含量调节,是蛋白质吸附的关键决定因素.
- 这种蛋白质吸附随后会影响巨细胞对DPPC/Chol脂质体的细胞吸收效率.
- 在脂质体配方中优化胆固醇水平可以提高它们对肺部疾病的治疗潜力,这些疾病需要向巨细胞.
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