Park Sehee, Ha My Kieu, Lee Yangsoon, Song Jaewoo, Yoon Tae Hyun
Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea.
Department of Laboratory Medicine, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea.
ACS Nanosci Au. 2023 Apr 24;3(4):323-334. doi: 10.1021/acsnanoscienceau.3c00001. eCollection 2023 Aug 16.
Understanding how nanoparticles (NPs) interact with biological systems is important in many biomedical research areas. However, the heterogeneous nature of biological systems, including the existence of numerous cell types and multitudes of key environmental factors, makes these interactions extremely challenging to investigate precisely. Here, using a single-cell-based, high-dimensional mass cytometry approach, we demonstrated that the presence of protein corona has significant influences on the cellular associations and cytotoxicity of gold NPs for human immune cells, and those effects vary significantly with the types of immune cells and their subsets. The altered surface functionality of protein corona reduced the cytotoxicity and cellular association of gold NPs in most cell types (e.g., monocytes, dendritic cells, B cells, natural killer (NK) cells, and T cells) and those immune cells selected different endocytosis pathways such as receptor-mediated endocytosis, phagocytosis, and micropinocytosis. However, even slight alterations in the major cell type (phagocytic cells and non-phagocytic cells) and T cell subsets (e.g., memory and naive T cells) resulted in significant protein corona-dependent variations in their cellular dose of gold NPs. Especially, naive T killer cells exhibited additional heterogeneity than memory T killer cells, with clusters exhibiting distinct cellular association patterns in single-cell contour plots. This multi-parametric analysis of mass cytometry data established a conceptual framework for a more holistic understanding of how the human immune system responds to external stimuli, paving the way for the application of precisely engineered NPs as promising tools of nanomedicine under various clinical settings, including targeted drug delivery and vaccine development.
了解纳米颗粒（NPs）如何与生物系统相互作用在许多生物医学研究领域都很重要。然而，生物系统的异质性，包括多种细胞类型的存在和众多关键环境因素，使得精确研究这些相互作用极具挑战性。在这里，我们使用基于单细胞的高维质谱流式细胞术方法证明，蛋白质冠层的存在对金纳米颗粒与人类免疫细胞的细胞结合和细胞毒性有显著影响，并且这些影响因免疫细胞类型及其亚群而异。蛋白质冠层改变的表面功能降低了金纳米颗粒在大多数细胞类型（如单核细胞、树突状细胞、B细胞、自然杀伤（NK）细胞和T细胞）中的细胞毒性和细胞结合，并且这些免疫细胞选择了不同的内吞途径，如受体介导的内吞作用、吞噬作用和微胞饮作用。然而，即使主要细胞类型（吞噬细胞和非吞噬细胞）和T细胞亚群（如记忆性和初始T细胞）有轻微改变，也会导致其金纳米颗粒细胞剂量中显著的蛋白质冠层依赖性变化。特别是，初始T杀伤细胞比记忆T杀伤细胞表现出更多的异质性，在单细胞等高线图中，细胞簇表现出不同的细胞结合模式。这种对质谱流式细胞术数据的多参数分析为更全面地理解人类免疫系统如何对外界刺激做出反应建立了一个概念框架，为在各种临床环境下，包括靶向药物递送和疫苗开发中，将精确工程化的纳米颗粒作为有前途的纳米医学工具的应用铺平了道路。
