Kimura Niko, Yamanishi Yoko, Sakuma Shinya
Department of Applied Chemistry, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
Division of Advanced Mechanical Systems Engineering, Institute of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei-shi, Tokyo, 184-8588, Japan.
Small. 2025 Sep;21(35):e2503749. doi: 10.1002/smll.202503749. Epub 2025 Jun 9.
Visualization of intercellular communication provides a means for understanding and leveraging complicated multicellular organizations. Various nanometer-sized artifacts (nano-artifacts) can be employed as small tracers for visualization, achieving spatially and temporally controlled intervention of these small tracers in the interactions remains challenging due to their diffusion-based transportation. To achieve spatiotemporally controlled visualization, cytotransducers are conceptualized that convert veiled intra/intercellular information into visible information. A 110-mm cytotransducer is presented, composed of a lipid layer and a fluorescent nanodiamond. The designed lipid layer allows effective uptake of the cytotransducer by neutrophils, and the fluorescent nanodiamond is labeled with the pH-responsive chemical fluorescein isothiocyanate to visualize the intracellular local pH at the single-cell level. Utilizing cytotransducers, cross-scale visualization of intercellular communication between neutrophils and three types of cells: macrophages, aged cells, and mesenchymal stem cells is demonstrated. Intracellular pH maps are obtained before and during the interactions, achieving spatiotemporally controlled visualization of intercellular communication based on the localized release of cytotransducers by programmed cell death (NETosis). A well-designed cytotransducer allows the simultaneous visualization of intra/intercellular information under spatiotemporally controlled conditions.
细胞间通讯的可视化提供了一种理解和利用复杂多细胞组织的方法。各种纳米尺寸的人工制品（纳米制品）可作为小型示踪剂用于可视化，然而，由于它们基于扩散的运输方式，要在这些小型示踪剂的相互作用中实现时空可控的干预仍然具有挑战性。为了实现时空可控的可视化，人们提出了细胞传感器的概念，它可以将隐藏的细胞内/细胞间信息转化为可见信息。本文展示了一种110毫米的细胞传感器，它由脂质层和荧光纳米金刚石组成。设计的脂质层能使中性粒细胞有效摄取细胞传感器，荧光纳米金刚石用pH响应化学物质异硫氰酸荧光素标记，以在单细胞水平上可视化细胞内局部pH值。利用细胞传感器，展示了中性粒细胞与三种类型细胞（巨噬细胞、衰老细胞和间充质干细胞）之间细胞间通讯的跨尺度可视化。在相互作用之前和期间获得细胞内pH图，基于程序性细胞死亡（中性粒细胞胞外诱捕网形成）引起的细胞传感器局部释放，实现了细胞间通讯的时空可控可视化。精心设计的细胞传感器能够在时空可控的条件下同时可视化细胞内/细胞间信息。
