探索脂质纳米颗粒对蛋白质稳定性和细胞蛋白质稳定性的影响
Zifan Gao1, Biao Jing2, Yuhui Wang3
1Dalian Medical University, Dalian 116044, China.
Journal of colloid and interface science
|August 31, 2024
概括
脂质纳米颗粒 (LNP) 可以破坏蛋白质的稳定,并在细胞中引起聚合,影响蛋白质平衡. 这项研究揭示了来自LNP的微妙蛋白质组应激,即使没有明显的细胞损伤,也突出了纳米毒性问题.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术纳米技术
- 分子生物学分子生物学
背景情况:
- 脂质纳米颗粒 (LNP) 对于药物输送至关重要,包括mRNA疫苗和基因编辑疗法.
- 虽然LNP通常是安全的,但其潜在的纳米毒性需要进行彻底的调查.
- 了解LNP与生物系统的相互作用对于治疗开发至关重要.
研究的目的:
- 为了研究LNP在体外蛋白质稳定性的影响.
- 评估LNP对HepG2细胞中细胞蛋白质稳态 (蛋白质稳态) 的影响.
- 探索LNP诱导的蛋白质组应激背后的分子机制.
主要方法:
- 在细胞溶解物和血中评估蛋白质稳定性,使用具有不同聚乙烯糖醇 (PEG) 比率的LNP.
- 使用AggStain光染料在HepG2细胞中的量化全球蛋白质组聚.
- 用AggRetina传感器测量了细胞微环境极性.
- 通过RNA测序 (RNA-Seq) 分析基因表达的变化,以确定蛋白质稳定路径激活.
主要成果:
- LNP降低了蛋白质的稳定性,增加了缓冲体和血中的聚合倾向.
- 在HepG2细胞中,LNP诱导全球蛋白质组聚.
- 细胞微环境极性降低,可能是由于LNP疏水成分.
- RNA-Seq揭示了展开蛋白质反应 (UPR) 和其他蛋白质稳定基因的激活.
结论:
- 这种LNP会损害蛋白质的稳定性,并诱导蛋白质组聚合.
- 通过破坏细胞蛋白质稳定,LNP可能会引起微妙的蛋白质组应激.
- 这些效应即使在没有显著损害细胞活力的情况下也会发生,这表明需要仔细的纳米毒性评估.
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