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

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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.