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基化纳米颗粒与巨细胞相互作用,独立于免疫反应因子,并触发非细胞,低炎症反应

Monireh Asoudeh¹, Nicole Nguyen², Mitch Raith¹

¹Department of Chemical and Biomolecular Engineering, University of Tennessee, Knoxville, TN 37996, USA.

Journal of controlled release : official journal of the Controlled Release Society

|December 20, 2023

概括

基于聚乙烯糖醇 (PEG) 的纳米颗粒并不是主要通过 opsonization 和 phagocytosis 与巨细胞相互作用. 相反,它们与脂蛋白受体结合,影响巨细胞的行为和肝脏积累.

科学领域:

生物医学工程生物医学工程
纳米技术纳米技术
免疫学免疫学免疫学

背景情况:

基于聚乙烯糖醇 (PEG) 的纳米粒子 (NP) 在药物输送中得到广泛使用.
它们的快速肝脏积累往往归因于opsonization和巨细胞消化.
这项研究研究了PEG-NP-巨细胞相互作用的潜在机制.

研究的目的:

挑战PEG-NP清除的传统的opsonization-phagocytosis假设.
确定参与PEG-NP-巨细胞相互作用的主要受体和途径.
阐明PEG-NP结合对巨细胞功能的下游影响.

主要方法:

评估小鼠和人类血液中对PEG-NP的蛋白质亲和力.
评估PEG-NP与有或没有血清蛋白质的巨细胞的结合.
研究脂蛋白对PEG-NP-巨细胞结合的影响.
在暴露于PEG-NP,脂蛋白,LPS和病原体后分析巨细胞的转录特征.
测量自细胞水平和细胞因子/化学因子从巨细胞分泌.

主要成果:

在没有血清的情况下,PEG-NPs对血液蛋白和结合巨细胞的亲和力是微不足道的.
脂蛋白抑制了PEG-NP与巨细胞的结合.
PEG-NPs诱导的巨细胞转录模式类似于脂蛋白,不同于LPS和病原体.
与LPS和病原体不同,PEG-NPs没有显著增加细胞化或炎症标志物.
高密度脂蛋白 (HDL) 和球形NP (SNP) 引起了类似的巨细胞转录反应.

结论:

冲化-细胞化途径不是PEG-NP-巨细胞相互作用的主要驱动因素.
PEG-NP与巨细胞上的 (apo) 脂蛋白和食尸体受体强烈相互作用.
这些受体相互作用调解PEG-NP结合,吸收和细胞效应.
这些受体在肝脏巨细胞和鼻状内皮细胞上的丰富性可能解释了肝脏快速积累.

关键词:

自自是一种自的过程.炎症炎症是一种炎症.脂质蛋白是一种脂质蛋白.脂质细胞体中的脂肪体.巨细胞是一个巨细胞.这就是PEG PEG PEG.发细胞症 (phagocytosis) 是一种致死细胞的发生.

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