Integrated three-dimensional (3D) microscopy for a spatial pharmacology atlas of macromolecular drugs in the tissue microenvironment

用于组织微环境中大分子药物空间药理学图谱的集成三维 (3D) 显微镜

• 批准号: 10275141
• 负责人: Steve Seung-Young Lee
• 金额: $ 39.36万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-24 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10275141
• 关键词: 3-Dimensional; Atlases; Biological; Biological Assay; Blood; Cell Communication; Cells; Collection; Disease; Goals; Image; Maps; Methodology; Methods; Microscopy; Molecular; Mus; Organ; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Reference Standards; Resolution; Science; Solid; Specimen; Tissues; cell type; human disease; insight; mouse model; pharmacokinetics and pharmacodynamics; preclinical development; research and development; response

Project Summary The goal of this project is to develop a new tissue assay method that permits single-cell resolution pharmacokinetics (PK) and pharmacodynamics (PD) profiling of macromolecular drugs in the spatial context of the organ-specific tissue microenvironment in both healthy and diseased states. With the integrated 3D microscopy, we will 1) map blood vasculature and transvascular transport of macromolecular drugs; 2) image the distribution and interaction of macromolecular drugs with multiple cell types in the tissue microenvironment; 3) determine cellular responses to macromolecular drugs in sub-microenvironment regions at the molecular level. This high-resolution 3D multiplex microscopy method will advance “Spatial Pharmacology” in the pharmaceutical sciences by enabling the mapping of the transport, distribution, and biological actions of macromolecular drugs in tissue specimens at the tissue-wide, cellular and molecular levels. The maps will provide new insights into transvascular transport of macromolecular drugs, drug-cell interactions, and biological responses of various cells to drugs in different sub-microenvironment regions of an organ. The collection of the maps, The Atlas of Spatial Pharmacology, will be a solid standard reference in the research and preclinical development of macromolecular drugs.

项目概要 该项目的目标是开发一种新的组织测定方法，允许单细胞分辨率 大分子药物在空间背景下的药代动力学 (PK) 和药效学 (PD) 分析 健康和患病状态下的器官特异性组织微环境。 显微镜下，我们将 1) 绘制血管图和大分子药物的跨血管运输图 2) 图像； 大分子药物在组织微环境中与多种细胞类型的分布和相互作用； 3）在分子水平上确定亚微环境区域中细胞对大分子药物的反应。 这种高分辨率 3D 多重显微镜方法将推进制药领域的“空间药理学” 通过绘制大分子药物的运输、分布和生物作用图谱来实现科学 这些图谱将为组织样本在组织范围、细胞和分子水平上提供新的见解。 大分子药物的血管转运、药物与细胞的相互作用以及各种细胞的生物反应 器官不同亚微环境药物区域的地图集，空间图集。 药理学，将成为大分子研究和临床前开发的坚实标准参考 药物。