Lee Henry, Vanhecke Dimitri, Balog Sandor, Taladriz-Blanco Patricia, Petri-Fink Alke, Rothen-Rutishauser Barbara
Adolphe Merkle Institute, University of Fribourg, Switzerland Chemin des Verdiers 4 Fribourg Switzerland
Department of Chemistry, University of Fribourg Chemin du Musée 9 Fribourg Switzerland.
Nanoscale Adv. 2024 Jul 1;6(18):4572-4582. doi: 10.1039/d4na00104d. eCollection 2024 Sep 10.
Macrophages play a pivotal role in the internalization and processing of administered nanoparticles (NPs). Furthermore, the phagocytic capacity and immunological properties of macrophages can vary depending on their microenvironment, exhibiting a spectrum of polarization states ranging from pro-inflammatory M1 to anti-inflammatory M2. However, previous research investigating this phenotype-dependent interaction with NPs has predominantly relied on semi-quantitative techniques or conventional metrics to assess intracellular NPs. Here, we focus on the interaction of human monocyte-derived macrophage phenotypes (M1-like and M2-like) with gold NPs (AuNPs) by combining population-based metrics and single-cell analysis by focused ion beam-scanning electron microscopy (FIB-SEM). The multimodal analysis revealed phenotype-dependent response and uptake behavior differences, becoming more pronounced after 48 hours. The study also highlighted phenotype-dependent cell-to-cell heterogeneity in AuNPs uptake and variability in particle number at the single-cell level, which was particularly evident in M2-like macrophages, which increases with time, indicating enhanced heteroscedasticity. Future efforts to design NPs targeting macrophages should consider the phenotypic variations and the distribution of NPs concentrations within a population, including the influence of cell-to-cell heterogeneity. This comprehensive understanding will be critical in developing safe and effective NPs to target different macrophage phenotypes.
巨噬细胞在给药纳米颗粒（NPs）的内化和处理过程中发挥着关键作用。此外，巨噬细胞的吞噬能力和免疫特性会因其微环境的不同而有所变化，呈现出从促炎性M1到抗炎性M2的一系列极化状态。然而，以往研究这种与NPs的表型依赖性相互作用时，主要依赖半定量技术或传统指标来评估细胞内的NPs。在此，我们通过结合基于群体的指标和聚焦离子束扫描电子显微镜（FIB-SEM）的单细胞分析，重点研究人单核细胞衍生的巨噬细胞表型（M1样和M2样）与金纳米颗粒（AuNPs）的相互作用。多模态分析揭示了表型依赖性的反应和摄取行为差异，在48小时后变得更加明显。该研究还强调了在AuNPs摄取方面表型依赖性的细胞间异质性以及单细胞水平上颗粒数量的变异性，这在M2样巨噬细胞中尤为明显，且随时间增加，表明异方差性增强。未来设计靶向巨噬细胞的NPs时，应考虑表型变化以及群体内NPs浓度的分布，包括细胞间异质性的影响。这种全面的理解对于开发针对不同巨噬细胞表型的安全有效的NPs至关重要。
