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相关实验视频

Updated: Jun 12, 2025

Nanosponge Tunability in Size and Crosslinking Density
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通过制造工艺量身定制脂质纳米粒子尺寸.

Caitlin McMillan1, Amy Druschitz2, Stephen Rumbelow2

  • 1University of Strathclyde Glasgow UK yvonne.perrie@strath.ac.uk.

RSC pharmaceutics
|September 26, 2024
PubMed
概括

调整脂质纳米颗粒 (LNP) 配方精确控制颗粒大小,影响mRNA表达. 较大的LNP在细胞和小鼠中表达的增加,高达120nm,挑战了传统的较小尺寸.

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科学领域:

  • 生物技术是生物技术.
  • 纳米医学是一种纳米医学.
  • 药物运输 药物运输 药物运输

背景情况:

  • 脂质纳米颗粒 (LNP) 是核酸治疗的关键输送载体,包括mRNA和siRNA.
  • 物理化学性质,如大小,封装和电荷,显著影响了LNP的疗效.
  • 目前的LNP配方通常使用大小小小于100 nm.

研究的目的:

  • 调查水分与脂质相比对LNP大小和关键质量属性的影响.
  • 评估不同的LNP大小如何影响mRNA表达在体外和体内.
  • 为了确定最佳的LNP大小范围以提高治疗疗效.

主要方法:

  • 使用ALC-0315与受控的水性与有机性脂质相比的NLP的配方.
  • 描述LNP大小和其他关键质量属性.
  • 在HEK293和THP-1细胞中的体外表达研究.
  • 在BALB/c小鼠体内表达的研究.

主要成果:

  • 通过调整相位比率来实现对LNP大小的精确控制.
  • 在HEK293细胞中,在LNP大小和mRNA表达之间观察到线性相关性.
  • 在THP-1细胞中,LNP的最大表达是120nm.

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  • 在小鼠体内研究表明,LNP>120nm的表达减少,在60-120nm之间表达强.

    • 结论:

    • 通过相比调整,可以精确调整LNP大小.
    • 在LNP中,mRNA载荷的表达表明了尺寸依赖的效应,其强度高达120nm.
    • 这些发现表明,较大的LNP (>100 nm) 可能提供更好的治疗潜力.