PEGylated nanoparticles interact with macrophages independently of immune response factors and trigger a non-phagocytic, low-inflammatory response.
PEGylated nanoparticles interact with macrophages independently of immune response factors and trigger a non-phagocytic, low-inflammatory response.
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聚乙二醇化纳米粒子与巨噬细胞相互作用，独立于免疫反应因子，并引发非吞噬性、低炎症反应。
DOI：
10.1016/j.jconrel.2023.12.019
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Da
中科院分区：
文献类型：
--
作者：
Asoudeh,Monireh;Nguyen,Nicole;Raith,Mitch;Denman,DesireeS;Anozie,UcheC;Mokhtarnejad,Mahshid;Khomami,Bamin;Skotty,KaitlynM;Isaac,Sami;Gebhart,Taylor;Vaigneur,Lauren;Gelgie,Aga;Dego,OudessaKerro;Freeman,Trevor;Beever,Jon;Da
基于聚乙二醇（PEG）的纳米颗粒（NP）-包括圆柱形胶束（CNP）、球形胶束（SNP）和聚乙二醇化脂质体（PL）-被假设通过调理作用随后通过肝巨噬细胞吞噬作用在体内被清除。该假设已被用于解释在施用到哺乳动物脉管系统中之后NP快速且显著地定位到肝脏。在这里，我们表明，调理作用-吞噬作用的关系不是驱动PEG-NP -巨噬细胞相互作用的主要因素。首先，小鼠和人类血液蛋白对PEG-NP的亲和力不显著。第二，PEG-NP在不存在血清蛋白的情况下结合巨噬细胞。第三，脂蛋白阻断PEG-NP与巨噬细胞的结合。由于这些发现，我们测试了PEG-NPs结合（载脂蛋白）脂蛋白受体的假设。事实上，PEG-NPs触发了体外巨噬细胞转录程序，该程序类似于由脂蛋白触发的程序，而不同于由脂多糖（LPS）和A组蛋白触发的程序。与LPS和病原体不同，PL不增加参与吞噬或炎症的转录物。高密度脂蛋白（HDL）和单核苷酸多态性触发非常相似的小鼠骨髓衍生的巨噬细胞转录程序。与调理的病原体不同，CNP、SNP和PL降低了巨噬细胞自噬体水平，并且减少或不增加关键巨噬细胞促炎细胞因子和趋化因子的分泌。因此，顺序调理和吞噬过程可能是PEG-NP -巨噬细胞相互作用的次要方面。相反，PEG-NP与（载脂蛋白）脂蛋白和清道夫受体的相互作用似乎是PEG-NP -巨噬细胞结合，进入和下游效应的强大驱动力。我们推测，这些受体在肝巨噬细胞和肝窦内皮细胞上的高存在是PEG-NPs快速且强烈地定位于肝脏的原因。
Poly-ethylene-glycol (PEG)-based nanoparticles (NPs) - including cylindrical micelles (CNPs), spherical micelles (SNPs), and PEGylated liposomes (PLs) - are hypothesized to be cleared in vivo by opsonization followed by liver macrophage phagocytosis. This hypothesis has been used to explain the rapid and significant localization of NPs to the liver after administration into the mammalian vasculature. Here, we show that the opsonization-phagocytosis nexus is not the major factor driving PEG-NP – macrophage interactions. First, mouse and human blood proteins had insignificant affinity for PEG-NPs. Second, PEG-NPs bound macrophages in the absence of serum proteins. Third, lipoproteins blocked PEG-NP binding to macrophages. Because of these findings, we tested the postulate that PEG-NPs bind (apo)lipoprotein receptors. Indeed, PEG-NPs triggered an in vitro macrophage transcription program that was similar to that triggered by lipoproteins and different from that triggered by lipopolysaccharide (LPS) and group AStreptococcus. Unlike LPS and pathogens, PLs did not increase transcripts involved in phagocytosis or inflammation. High-density lipoprotein (HDL) and SNPs triggered remarkably similar mouse bone-marrow-derived macrophage transcription programs. Unlike opsonized pathogens, CNPs, SNPs, and PLs lowered macrophage autophagosome levels and either reduced or did not increase the secretion of key macrophage pro-inflammatory cytokines and chemokines. Thus, the sequential opsonization and phagocytosis process is likely a minor aspect of PEG-NP – macrophage interactions. Instead, PEG-NP interactions with (apo)lipoprotein and scavenger receptors appear to be a strong driving force for PEG-NP – macrophage binding, entry, and downstream effects. We hypothesize that the high presence of these receptors on liver macrophages and on liver sinusoidal endothelial cells is the reason PEG-NPs localize rapidly and strongly to the liver.
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