在哺乳动物细胞中提供mRNA的Zwitterionic聚合物装饰脂质纳米颗粒
Phim-On Khunsuk1, Chitsuda Pongma2, Tanapat Palaga3,4
1Program in Petrochemistry and Polymer Science, Faculty of Science, Chulalongkorn University, Phayathai Road, Pathumwan, Bangkok 10330, Thailand.
Biomacromolecules
|November 13, 2023
概括
研究人员使用zwitterionic聚合物开发了非聚乙烯甘醇 (PEG) 脂质纳米粒子 (LNPs). 这些PMPC-LNP显示出作为安全有效的mRNA载体的承诺,克服PEG过敏挑战.
科学领域:
- 生物技术是生物技术.
- 材料科学 材料科学 材料科学
- 纳米医学是一种纳米医学.
背景情况:
- 脂质纳米颗粒 (LNP) 对于mRNA传递至关重要.
- 聚乙烯甘醇 (PEG) 涂层增强了LNP的稳定性,但可以引起免疫反应 (PEG过敏).
- 开发非PEG替代品对于更安全的mRNA疫苗和治疗方法至关重要.
研究的目的:
- 使用zwitterionic聚合物创建和评估新的非PEG脂质纳米颗粒.
- 评估这些新型LNP的物理化学特性,生物相容性和mRNA转染效率.
- 为了证明zwitterionic聚合物结合的LNP作为先进的mRNA载体的潜力.
主要方法:
- 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) 与具有不同链长的多-2-methyacryloyloxyethyl phosphorylcholine (PMPC) 的结合.
- 制定PMPC-LNP及其大小,电荷,稳定性和隐形性的特征.
- 使用HEK293T细胞进行PMPC-LNP细胞毒性的体外评估,使用THP-1细胞进行炎症反应.
- 与传统的PEG-LNP相比,mRNA转染效率的评估.
主要成果:
- 球形PMPC-LNPs (144-255nm) 具有中性电荷和良好的稳定性 (28天在4°C) 已成功形成.
- PMPC涂料表现出显著的防性质,实现了近乎完美的隐形性.
- PMPC-LNPs对HEK293T细胞没有表现出毒性,也没有诱导THP-1细胞的炎症反应.
- PMPC-LNP的mRNA转染效率超过了PEG-LNP的效率.
结论:
- 基聚合物结合的DPE-PMPC脂质有效地形成稳定,无毒的LNP.
- 与PEG-LNP相比,这些PMPC-LNP提供了优越的mRNA传递性能.
- 开发的PMPC-LNPs代表了基于mRNA的疗法和疫苗的有希望的,潜在的低过敏替代品.
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