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: 10727015
• 负责人: Steve Seung-Young Lee
• 金额: $ 3.61万
• 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/10727015
• 关键词: 3-Dimensional; Atlases; Biological; Biological Assay; Blood; Blood Vessels; 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.

项目总结